The use of an evidence based approach to guide optimal surgical management of colorectal liver metastases

The aim of this thesis was to validate the optimal surgical management of colorectal liver metastases (CLM) by using an evidence based approach. A meta-analysis comparing combined and sequential resection for synchronous CLM demonstrated that combined resection is associated with reduced hospital stay and with comparable perioperative mortality and morbidity, operative blood loss, and survival rates as sequential resection. Nevertheless, combined resection was associated with lower metastatic disease severity compared to sequential resection. A meta-analysis assessed liver resection for CLM in the presence of hepatic lymph node involvement and demonstrated that survival rates are lower in node positive disease patients compared to node negative disease patients, irrespective of whether the positive disease nodes were detected by routine or selective lymphadenectomy, or whether nodal involvement was microscopic or macroscopic. A network meta-analysis comparing different treatment strategies aiming to decrease operative blood loss found no difference in mortality, length of hospital stay or ITU stay between the treatment strategies. The use of radiofrequency dissecting sealer resulted in more serious adverse events compared to the clamp-crush method in the absence of vascular occlusion and fibrin sealant. Simple methods, such as clamp-crush method, gave overall equivalent outcomes to methods which require special equipment. Not reporting the period of follow-up was investigated as a potential source of study bias. Overall analysis did not identify a significant difference in mortality and disease recurrence, but sensitivity analysis of more recent reviews and larger reviews showed that the trials reporting the period of follow-up had a significantly lower hazard ratio for disease recurrence compared to trials not reporting the period of follow-up. A network meta-analysis comparing interventions aiming to decrease ischaemia-reperfusion injury during liver resection, demonstrated that ischaemic preconditioning resulted in fewer serious adverse events, lower operative blood loss, fewer transfusion proportions, and shorter operative time

A network meta-analysis comparing perioperative outcomes of interventions aiming to decrease ischemia reperfusion injury during elective liver resection

OBJECTIVE: This study sought to compare the perioperative outcomes of interventions aiming to decrease ischemia-reperfusion (IR) injury during elective liver resection. METHOD: A comprehensive literature search was performed to identify randomized controlled trials. A Bayesian network metaanalysis was performed using the Markov chain Monte Carlo method in WinBUGS following the guidelines of the National Institute for Health and Clinical Excellence Decision Support Unit. Odds ratios for binary outcomes and mean differences for continuous outcomes were calculated using a fixed effect model or a random effects model according to model fit. RESULTS: Forty-four trials with 2,457 patients having undergone liver resection were included and were divided into 8 classes of interventions aimed at decreasing IR injury and a control group, which was hepatectomy alone. There was no difference between the different interventions in mortality, quantity of blood transfusion, and durations of stay in an intensive therapy unit between any pairwise comparisons. Patients treated with ischemic preconditioning, cardiovascular modulators, and miscellaneous interventions had significantly fewer serious adverse events compared with patients undergoing liver resection alone. Ischemic preconditioning patients had significantly fewer transfusion proportions and shorter operative time than patients treated with steroids. Ischemic preconditioning had significantly less operative blood loss compared with all other interventions, and a lesser duration of hospital stay than hepatectomy alone. Sensitivity analysis showed that the drugs sevoflurane (a volatile anesthetic), verapamil (a calcium channel blocker), and gabexate mesilate (a thrombin inhibitor) produced fewer serious adverse events compared with hepatectomy alone. CONCLUSION: Ischemic preconditioning resulted in multiple beneficial clinical endpoints and further RCTs seem to be needed to confirm its clinical benefits

Functional outcomes with handsewn versus stapled anastomoses in the treatment of ultralow rectal cancer

Adequate oncological outcomes have been demonstrated with rectal resection and handsewn coloanal anastomosis (CAA) in tumours in close proximity to the internal anal sphincter. Our aim was to assess functional differences between handsewn CAA and ultralow stapled anastomosis. Participants were identified from a single-surgeon series. Included participants underwent anorectal physiology testing of anal sphincter function, in addition to completion of several questionnaires: Wexner Incontinence Score (WIS); Birmingham Bowel, Bladder and Urinary Symptom Questionnaire (BBUSQ); Low Anterior Resection Syndrome (LARS) Score; SF36. Non-parametric data compared using the Mann-Whitney U test. 20 participants were included; 11 stapled and 9 handsewn. Mean follow-up was 2.95 ± 1.97 years. The mean LARS score was 21.9 ± 1.97 years in the stapled group versus 29.4 ± 9.57 in the handsewn group (p = 0.133). The Wexner incontinence score was significantly higher in the handsewn group (p = 0.0076), with a mean score of 4.6 ± 3.69 versus 10.9 ± 4.76. The incontinence domain of the BBUSQ was also significantly worse in patients with a handsewn anastomosis (p = 0.001). With the exception of general health (p = 0.035) and social functioning (p = 0.035), which were worse in the handsewn groups, the other six domains of the SF-36 showed no statistical difference between groups. Anorectal physiology scores were not significantly different. Handsewn CAA anastomosis is known to be safe and oncologically feasible. Patient selection should be vigorous, with preoperative counseling regarding the likelihood of incontinence to manage patients' expectations and promote comparable quality of life in the long-term

Methods to decrease blood loss during liver resection: a network meta-analysis

BACKGROUND: Liver resection is a major surgery with significant mortality and morbidity. Specialists have tested various methods in attempts to limit blood loss, transfusion requirements, and morbidity during elective liver resection. These methods include different approaches (anterior versus conventional approach), use of autologous blood donation, cardiopulmonary interventions such as hypoventilation, low central venous pressure, different methods of parenchymal transection, different methods of management of the raw surface of the liver, different methods of vascular occlusion, and different pharmacological interventions. A surgeon typically uses only one of the methods from each of these seven categories. The optimal method to decrease blood loss and transfusion requirements in people undergoing liver resection is unknown. OBJECTIVES: To assess the effects of different interventions for decreasing blood loss and blood transfusion requirements during elective liver resection. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Science Citation Index Expanded to September 2015 to identify randomised clinical trials. We also searched trial registers and handsearched the references lists of identified trials. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or publication status) comparing different methods of decreasing blood loss and blood transfusion requirements in people undergoing liver resection. DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials and collected data. We assessed the risk of bias using Cochrane domains. We conducted a Bayesian network meta-analysis using the Markov chain Monte Carlo method in WinBUGS 1.4, following the guidelines of the National Institute for Health and Care Excellence Decision Support Unit guidance documents. We calculated the odds ratios (OR) with 95% credible intervals (CrI) for the binary outcomes, mean differences (MD) with 95% CrI for continuous outcomes, and rate ratios with 95% CrI for count outcomes, using a fixed-effect model or random-effects model according to model-fit. We assessed the evidence with GRADE. MAIN RESULTS: We identified 67 randomised clinical trials involving a total of 6197 participants. All the trials were at high risk of bias. A total of 5771 participants from 64 trials provided data for one or more outcomes included in this review. There was no evidence of differences in most of the comparisons, and where there was, these differences were in single trials, mostly of small sample size. We summarise only the evidence that was available in more than one trial below. Of the primary outcomes, the only one with evidence of a difference from more than one trial under the pair-wise comparison was in the number of adverse events (complications), which was higher with radiofrequency dissecting sealer than with the clamp-crush method (rate ratio 1.85, 95% CrI 1.07 to 3.26; 250 participants; 3 studies; very low-quality evidence). Among the secondary outcomes, the only differences we found from more than one trial under the pair-wise comparison were the following: blood transfusion (proportion) was higher in the low central venous pressure group than in the acute normovolemic haemodilution plus low central venous pressure group (OR 3.19, 95% CrI 1.56 to 6.95; 208 participants; 2 studies; low-quality evidence); blood transfusion quantity (red blood cells) was lower in the fibrin sealant group than in the control (MD -0.53 units, 95% CrI -1.00 to -0.07; 122 participants; 2; very low-quality evidence); blood transfusion quantity (fresh frozen plasma) was higher in the oxidised cellulose group than in the fibrin sealant group (MD 0.53 units, 95% CrI 0.36 to 0.71; 80 participants; 2 studies; very low-quality evidence); blood loss (MD -0.34 L, 95% CrI -0.46 to -0.22; 237 participants; 4 studies; very low-quality evidence), total hospital stay (MD -2.42 days, 95% CrI -3.91 to -0.94; 197 participants; 3 studies; very low-quality evidence), and operating time (MD -15.32 minutes, 95% CrI -29.03 to -1.69; 192 participants; 4 studies; very low-quality evidence) were lower with low central venous pressure than with control. For the other comparisons, the evidence for difference was either based on single small trials or there was no evidence of differences. None of the trials reported health-related quality of life or time needed to return to work. AUTHORS' CONCLUSIONS: Paucity of data meant that we could not assess transitivity assumptions and inconsistency for most analyses. When direct and indirect comparisons were available, network meta-analysis provided additional effect estimates for comparisons where there were no direct comparisons. However, the paucity of data decreases the confidence in the results of the network meta-analysis. Low-quality evidence suggests that liver resection using a radiofrequency dissecting sealer may be associated with more adverse events than with the clamp-crush method. Low-quality evidence also suggests that the proportion of people requiring a blood transfusion is higher with low central venous pressure than with acute normovolemic haemodilution plus low central venous pressure; very low-quality evidence suggests that blood transfusion quantity (red blood cells) was lower with fibrin sealant than control; blood transfusion quantity (fresh frozen plasma) was higher with oxidised cellulose than with fibrin sealant; and blood loss, total hospital stay, and operating time were lower with low central venous pressure than with control. There is no evidence to suggest that using special equipment for liver resection is of any benefit in decreasing the mortality, morbidity, or blood transfusion requirements (very low-quality evidence). Radiofrequency dissecting sealer should not be used outside the clinical trial setting since there is low-quality evidence for increased harm without any evidence of benefits. In addition, it should be noted that the sample size was small and the credible intervals were wide, and we cannot rule out considerable benefit or harm with a specific method of liver resection

Abdominal versus perineal approach for external rectal prolapse: systematic review with meta-analysis

BACKGROUND: External rectal prolapse (ERP) is a debilitating condition in which surgery plays an important role. The aim of this study was to evaluate the outcomes of abdominal approaches (AA) and perineal approaches (PA) to ERP. METHODS: This was a PRISMA-compliant systematic review with meta-analysis. Studies published between 1990 and 2021 were retrieved. The primary endpoint was recurrence at the last available follow-up. Secondary endpoints included factors associated with recurrence and function. All studies were assessed for bias using the Newcastle-Ottawa Scale and Cochrane tool. RESULTS: Fifteen studies involving 1611 patients (AA = 817; PA = 794) treated for ERP were included, three of which were randomized controlled trials (RCTs; 114 patients (AA = 54; PA = 60)). Duration of follow-up ranged from 12 to 82 months. Recurrence in non-randomized studies was 7.7 per cent in AA versus 20.1 per cent in PA (odds ratio (OR) 0.29, 95 per cent confidence interval (c.i.) 0.17 to 0.50; P < 0.001, I2 = 45 per cent). In RCTs, there was no significant difference (9.8 per cent versus 16.3 per cent, AA versus PA (OR 0.82, 95 per cent c.i. 0.29 to 2.37; P = 0.72, I2 = 0.0 per cent)). Age at surgery and duration of follow-up were risk factors for recurrence. Following AA, the recurrence rates were 10.1 per cent and 6.2 per cent in patients aged 65 years and older and less than 65 years of age, respectively (effect size [e.s.] 7.7, 95 per cent c.i. 4.5 to 11.5). Following PA, rates were 27 per cent and 16.3 per cent (e.s. 20.1, 95 per cent c.i. 13 to 28.2). Extending follow-up to at least 40 months increased the likelihood of recurrence. The median duration of hospital stay was 4.9 days after PA versus 7.2 days after AA. Overall, incontinence was less likely after AA (OR 0.32), but constipation occurred more frequently (OR 1.68). Most studies were retrospective, and several outcomes from RCTs were not consistent with those observed in non-RCTs. CONCLUSION: The overall risk of recurrence of ERP appears to be higher with PA versus AA. Incontinence is less frequent after AA but at the cost of increased constipation. Age at surgery and duration of follow-up are associated with increased risk of recurrence, which warrants adequate reporting of future studies on this topic

The role of Neurotensin and its receptors in non-gastrointestinal cancers: a review

Background Neurotensin, originally isolated in 1973 has both endocrine and neuromodulator activity and acts through its three main receptors. Their role in promoting tumour cell proliferation, migration, DNA synthesis has been studied in a wide range of cancers. Expression of Neurotensin and its receptors has also been correlated to prognosis and prediction to treatment. Main body The effects of NT are mediated through mitogen-activated protein kinases, epidermal growth factor receptors and phosphatidylinositol-3 kinases amongst others. This review is a comprehensive summary of the molecular pathways by which Neurotensin and its receptors act in cancer cells. Conclusion Identifying the role of Neurotensin in the underlying molecular mechanisms in various cancers can give way to developing new agnostic drugs and personalizing treatment according to the genomic structure of various cancers

After-hours colorectal surgery: a risk factor for anastomotic leakage

__Purpose:__ This study aims to increase knowledge of colorectal anastomotic leakage by performing an incidence study and risk factor analysis with new potential risk factors in a Dutch tertiary referral center. __Methods:__ All patients whom received a primary colorectal anastomosis between 1997 and 2007 were selected by means of operation codes. Patient records were studied for population description and risk factor analysis. __Results:__ In total 739 patients were included. Anastomotic leakage (AL) occurred in 64 (8.7%) patients of whom nine (14.1%) died. Median interval between operation and diagnosis was 8 days. The risk for AL was higher as the anastomoses were constructed more distally (p = 0.019). Univariate analysis showed duration of surgery (p = 0.038), BMI (p = 0.001), time of surgery (p = 0.029), prophylactic drainage (p = 0.006) and time under anesthesia (p = 0.012) to be associated to AL. Multivariate analysis showed BMI greater than 30 kg/m2(p = 0.006; OR 2.6 CI 1.3-5.2) and "after hours" construction of an anastomosis (p = 0.030; OR 2.2 CI 1.1-4.5) to be independent risk factors. __Conclusion:__ BMI greater than 30 kg/m2and "after hours" construction of an anastomosis were independent risk factors for colorectal anastomotic leakage

Perioperative outcome of laparoscopic left lateral liver resection is improved by using a bioabsorbable staple line reinforcement material in a porcine model

Hypothesis Laparoscopic liver surgery is significantly limited by the technical difficulty encountered during transection of substantial liver parenchyma, with intraoperative bleeding and bile leaks. This study tested whether the use of a bioabsorble staple line reinforcement material would improve outcome during stapled laparoscopic left lateral liver resection in a porcine model. Study design A total of 20 female pigs underwent stapled laparoscopic left lateral liver resection. In group A (n = 10), the stapling devices were buttressed with a bioabsorbable staple line reinforcement material. In group B (n = 10), standard laparoscopic staplers were used. Operative data and perioperative complications were recorded. Necropsy studies and histopathological analysis were performed at 6 weeks. Data were compared between groups with the Student's t-test or the chi-square test. Results Operating time was similar in the two groups (64 +/- 11 min in group A versus 68 +/- 9 min in group B, p = ns). Intraoperative blood loss was significantly higher in group B (185 +/- 9 mL versus 25 +/- 5 mL, p <0.05). There was no mortality. There was no morbidity in the 6-week follow-up period; however, two animals in group B had subphrenic bilomas (20%) at necropsy. At necropsy, methylene blue injection via the main bile duct revealed leakage from the biliary tree in four animals in group B and none in group A (p <0.05). Histopathological examination of the resection site revealed minor abnormalities in group A while animals in group B demonstrated marked fibrotic changes and damaged vascular and biliary endothelium. Conclusion Use of a bioabsorbable staple line reinforcement material reduces intraoperative bleeding and perioperative bile leaks during stapled laparoscopic left lateral liver resection in a porcine model

Management of intra-abdominal infections : recommendations by the WSES 2016 consensus conference

This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.Peer reviewe