Detection of Anastomotic Leakage Following Elective Colonic Surgery: Results of the Prospective Biomarkers and Anastomotic Leakage (BALL) Study.

BACKGROUND: Anastomotic leakage (AL) is an infrequent but life-threatening surgical complication following colorectal surgery. Early diagnosis remains clinically difficult but is a necessity to reduce associated morbidity and mortality. Clinical review and radiological modalities for the diagnosis of leakage remain non-specific and often only detect AL once it is well developed. Inflammatory biomarkers however have shown promise in early pre-clinical detection of leakage following colorectal surgery. METHODS: A multi-center, prospective observational study was conducted across four public hospitals in Auckland and Christchurch, New Zealand. Consecutive adults undergoing elective colectomy were initially recruited over a 3-y period. Perioperative blood samples were collected to measure interleukin (IL)-6, IL-1ß, tumor necrosis factor α, IL-10, C-reactive protein (CRP), leukocyte and neutrophil counts. Statistical analysis was performed to compare patients with an uncomplicated recovery with patients with AL. RESULTS: Sixteen patients developed AL (5.7%), diagnosed at a median post-operative (POD) day 7. CRP and IL-6 were consistently elevated in the early post-operative period in patients with AL, and had the best diagnostic accuracy on POD 3 (area under the curve 0.70; P = 0.02) and POD 1 (area under the curve 0.69; P = 0.02), respectively. IL-10, once adjusted for body mass index and surgical approach, was the sole biomarker significantly elevated in patients with AL on POD 4. CONCLUSIONS: Early post-operative elevations of CRP and IL-6 provide utility for early detection of AL after elective colectomy. Application of these inflammatory biomarkers and their combinations in daily practice warrants further investigation.

Antibiotics Do Not Reduce Length of Hospital Stay for Uncomplicated Diverticulitis in a Pragmatic Double-Blind Randomized Trial.

BACKGROUND & AIMS: Antibiotic treatment is the standard care for patients with uncomplicated acute diverticulitis. However, this practice is based on low-level evidence and has been challenged by findings from 2 randomized trials, which did not include a placebo group. We investigated the non-inferiority of placebo vs antibiotic treatment for the management of uncomplicated acute diverticulitis. METHODS: In the selective treatment with antibiotics for non-complicated diverticulitis study, 180 patients hospitalized for uncomplicated acute diverticulitis (determined by computed tomography, Hinchey 1a grade) from New Zealand and Australia were randomly assigned to groups given antibiotics (n = 85) or placebo (n = 95) for 7 days. We collected demographic, clinical, and laboratory data and answers to questionnaires completed every 12 hrs for the first 48 hrs and then daily until hospital discharge. The primary endpoint was length of hospital stay; secondary endpoints included occurrence of adverse events, readmission to the hospital, procedural intervention, change in serum markers of inflammation, and patient-reported pain scores at 12 and 24 hrs. RESULTS: There was no significant difference in median time of hospital stay between the antibiotic group (40.0 hrs; 95% CI, 24.4-57.6 hrs) and the placebo group (45.8 hrs; 95% CI, 26.5-60.2 hrs) (P = .2). There were no significant differences between groups in adverse events (12% for both groups; P = 1.0), readmission to the hospital within 1 week (1% for the placebo group vs 6% for the antibiotic group; P = .1), and readmission to the hospital within 30 days (11% for the placebo group vs 6% for the antibiotic group; P = .3). CONCLUSIONS: Foregoing antibiotic treatment did not prolong length of hospital admission. This result provides strong evidence for omission of antibiotics for selected patients with uncomplicated acute diverticulitis. ACTRN: 12615000249550.

Intravenous Local Anaesthetic Compared with Intraperitoneal Local Anaesthetic in Abdominal Surgery: A Systematic Review.

INTRODUCTION: Modern perioperative care strategies aim to optimise perioperative care by reducing the body's stress response to surgery. A major facet of optimising an abdominal surgery analgesia programme is using a multimodal opioid sparing approach. Local anaesthetics have shown promise and there has been considerable research into the most effective route for their administration. This review aims to determine if there is a difference in analgesic efficacy between intraperitoneal local anaesthetic (IPLA) and intravenous local anaesthetic (IVLA). MATERIALS AND METHODOLOGY: In concordance with the PRISMA statement, a literature search was conducted to identify randomised control trials that compared IVLA with IPLA in abdominal surgery. The primary outcomes of interest were opioid analgesia requirements and pain score assessed by visual analogue score. Data were extracted and entered into pre-designed electronic spreadsheets. RESULTS: This review has identified six papers that compared intravenous lignocaine to intraperitoneal lignocaine. This review showed significantly lower morphine consumption at 4 and 24 h in the intraperitoneal group. There was no significant difference in pain scores. CONCLUSION: From the analysis of these studies, intraperitoneal local anaesthetic had an analgesic benefit over intravenous lignocaine with regard to decreased opioid consumption for abdominal surgery. Further research investigating IVL combined with intraperitoneal local anaesthetic is warranted.

Optimal Dosing of Botulinum Toxin for Treatment of Chronic Anal Fissure: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic anal fissures are associated with significant morbidity and reduced quality of life. Studies have investigated the efficacy of botulinum toxin with variable results; thus, there is currently no consensus on botulinum toxin dose or injection sites. OBJECTIVE: This study aimed to systematically analyze trials studying the efficacy of botulinum toxin for treatment of chronic anal fissure to identify an optimum dosage and injection regimen. DATA SOURCES: A comprehensive review of the literature was conducted according to PRISMA guidelines. PubMed/Medline, Embase, Scopus, and the Cochrane Library were searched from inception to June 2015. STUDY SELECTION: All clinical trials that investigated the efficacy of botulinum toxin for chronic anal fissure were selected according to specific criteria. INTERVENSIONS: The interventions used were various doses of botulinum toxin. OUTCOME MEASURES: Clinical outcomes, dosage, and injection site data were evaluated with weighted pooled results for each dosage and 95% confidence intervals. RESULTS: There were 1158 patients, with 661 in botulinum toxin treatment arms, from 18 clinical trials included in this review. The outcomes of interest were 3-month healing, incontinence, and recurrence rates. Meta-regression analysis demonstrated a small decrease in healing rate (0.34%; 95% CI, 0-0.68; p = 0.048) with each increase in dosage, a small increase in incontinence rate (1.02 times; 95% CI, 1.0002-1.049; p = 0.048) with each increase in dosage and a small increase in recurrence rate (1.037 times; 95% CI, 1.018-1.057; p = 0.0002) with each increase in dosage. The optimum injection site could not be determined. LIMITATIONS: This study was limited by weaknesses in the underlying evidence, such as variable quality, short follow-up, and a limited range of doses represented. CONCLUSIONS: Fissure healing with lower doses of botulinum toxin is as effective as with high doses. Lower doses also reduce the risk of incontinence and recurrence in the long term.

Peritoneal Cytokine Levels Can Predict Anastomotic Leak on the First Postoperative Day.

BACKGROUND: Accumulating evidence suggests that peritoneal cytokine concentrations may predict anastomotic leak after colorectal surgery, but previous studies have been underpowered. OBJECTIVE: We aimed to test this hypothesis by using a larger prospectively collected data set. DESIGN: This study is an analysis of prospectively collected data. SETTINGS: This study was conducted at 3 public hospitals in Auckland, New Zealand. PATIENTS: Patients undergoing colorectal surgery recruited as part of 3 previous randomized controlled trials were included. MAIN OUTCOME MEASURES: Data on peritoneal and plasma levels of interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α on day 1 after colorectal surgery were reanalyzed to evaluate their predictive value for clinically important anastomotic leak. Area under receiver operating characteristic curve analysis was performed. RESULTS: A total of 206 patients with complete cytokine data were included. The overall anastomotic leak rate was 8.3%. Concentration levels of peritoneal interleukin-6 and interleukin-10 on day 1 after colorectal surgery were predictive of anastomotic leak (area under receiver operating characteristic curve, 0.72 and 0.74; p = 0.006 and 0.004). Plasma cytokine levels of interleukin-6 were higher on day 1 after colorectal surgery in patients who had an anastomotic leak, but this was a poor predictor of anastomotic leak. Levels of other peritoneal and plasma cytokines were not predictive. LIMITATIONS: The study was not powered a priori for anastomotic leak prediction. Although the current data do suggest that peritoneal levels of interleukin-6 and interleukin-10 are predictive of leak, the discriminative value in clinical practice remains unclear. CONCLUSIONS: Peritoneal levels of interleukin-6 and interleukin-10 on day 1 after colorectal surgery can predict clinically important anastomotic leak.

The effect of oral simvastatin on fibrinolytic activity after colorectal surgery-a pilot study.

BACKGROUND: Studies conducted in animal models have shown that statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) reduce adhesion formation by upregulating fibrinolysis. The aim of this study was to determine the effect of orally administered statins on the promoters and inhibitors of the fibrinolytic pathway. METHODS: In a previously described double-blinded clinical trial, 144 patients undergoing elective colorectal resection, or reversal of Hartmann's procedure were randomized to receive 40 mg once daily oral simvastatin 3-7 d before surgery or placebo. For the purposes of the present study, peritoneal drain fluid was collected postoperatively from patients to measure active tissue plasminogen activator (tPA), tissue plasminogen activator total antigen, active plasminogen activator inhibitor-1 (PAI-1), plasminogen activator inhibitor total antigen (PAI-1TA), plasminogen activator inhibitor-1 and tissue plasminogen activator complex (PAI-1/tPA). These were analyzed using ELISA. The number of hospitalizations and complications related to small bowel obstruction (SBO) were recorded at 2 y after surgery. RESULTS: A total of 95 patients (72%) had sufficient peritoneal drain fluid suitable for ELISA analysis. Of them, 46 patients (48%) were from the oral simvastatin group. Mean tPA and tPA total antigen concentrations in peritoneal fluid were similar between the two groups. Mean PAI-1 and PAI-1 TA concentrations in the statin and placebo group were also similar. Mean PAI-1/tPA complex concentration was similar between the two groups. The number of hospitalizations from SBOs were 5 and 4 in the statin and placebo groups respectively (P = 0.46). The overall mortality at 2-year post-surgery was similar between the two groups (P = 0.59). CONCLUSIONS: In this pilot study involving humans, oral simvastatin had no measured effect on the peritoneal fibrinolytic pathway in the first 24 h after colorectal surgery. Analysis of clinical outcomes also showed that oral simvastatin did not reduce hospitalizations for SBO in the 2 y after surgery. Further studies may be useful to evaluate whether fibrinolytic pathways beyond 24 h are altered after systemic administration of statins and to evaluate the use of higher doses of statins, perhaps used intraperitoneally rather than systemically.

Changing the routine: a move to patient initiated follow up to improve surgical outpatient clinic.

INTRODUCTION: Patient initiated follow up (PIFU) allows patients to initiate a hospital follow up appointment on an 'as required' basis in contrast to the traditional physician-initiated model. We present a clinical pathway for patients referred with rectal bleeding at a large tertiary public hospital in South Auckland, New Zealand and demonstrate the utility of PIFU and its impact on reducing follow up appointments. METHOD: The purpose of the pathway was to allow standardized care by the clinicians and allow for PIFU. Two separate protocols were developed - 'Painful PR bleeding' and 'Painless PR bleeding'. A new clinic (NC) was started following these protocols, and this was compared to historical controls (HC). The primary outcome was the rate of follow up appointments. RESULTS: There were 133 patients in the NC and 135 in the HC, with significantly less follow ups in the NC (6% versus 45%, p < 0.0001). A small percentage of patients in the NC group were directly discharged (10%) whilst 70% of patients were discharged with a PIFU card. Thirty phone calls were made using PIFU, with 10 patients returning to clinic and 20 requiring advice and reassurance only. At 5 year follow up, there was a single colorectal malignancy found in both groups. CONCLUSION: Initiating a protocol that includes patient initiated follow up vastly reduces the need for routine return to clinic for the majority of patients, without sacrificing patient care. A protocolised approach to clinic for other areas in general surgery should be considered.

Evaluation of the inflammatory profile following uncomplicated elective colectomy.

BACKGROUND: Attenuation of the inflammatory response in patients undergoing colectomy with modern perioperative care and laparoscopic surgery has been a focus of research in recent years. Despite reported benefits, significant heterogeneity remains with studies including patients undergoing both rectal and colon surgery and including surgery with postoperative complications. Therefore, the aim of the study was to evaluate the inflammatory response in patients undergoing elective colectomy without complications, specifically comparing open and laparoscopic approaches. METHODS: A multicenter prospective study was conducted across four public hospitals in Auckland and Christchurch, New Zealand. Consecutive adults undergoing elective colectomy were included over a 3-year period. Perioperative blood samples were collected and analysed for the following inflammatory markers: IL-6, IL-1ß, TNFα, IL-10, CRP, leucocyte and neutrophil count. Statistical analysis was performed using SPSS statistical software. RESULTS: A total of 168 colectomy patients without complications were included in the analysis. Patients that underwent laparoscopy had significantly reduced IL-6, neutrophils and CRP on postoperative day (POD) 1 (p < 0.05) compared to an open approach. IL-10 and TNFα were significantly reduced on POD 2 (p < 0.05) in laparoscopic patients. Patients with a Body Mass Index (BMI) greater than 30 kg/m2 had significantly higher levels of CRP regardless of operative approach. Statins altered both preoperative and postoperative inflammatory markers. CONCLUSION: The postoperative inflammatory response is influenced by surgical approach, perioperative medications, and patient factors. These findings have important implications in the utility of biomarkers in the diagnosis of postoperative surgical complications, in particular in the early diagnosis of anastomotic leak.

Diagnostic accuracy of procalcitonin for the early diagnosis of anastomotic leakage after colorectal surgery: a meta-analysis.

BACKGROUND: Anastomotic leakage (AL) is a dreaded complication following colorectal surgery. Procalcitonin is one of many biomarkers studied and research has suggested that it has improved accuracy for the diagnosis of AL compared with other inflammatory biomarkers such as C-reactive protein. This meta-analysis was conducted to evaluate the accuracy of procalcitonin in the early diagnosis of AL following colorectal surgery. METHODS: MEDLINE, Embase and PubMed were searched for studies evaluating procalcitonin in the context of AL following colorectal surgery in the elective setting. The literature was reviewed using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. Quality of the studies was assessed using the Quality Assessment Diagnostic Accuracy Studies (QUADAS)-2 tool. Meta analyses were conducted using area under the receiver operating characteristic curves for day 3, 4 and 5 post-surgery as a diagnostic test to detect AL. RESULTS: A total of eight studies were analysed. Results showed that the highest diagnostic accuracy for procalcitonin is on day 5 post surgery. The reported optimal cut-off values ranged from 0.25 to 680 ng/mL from postoperative day 3 to 5, with reported negative predictive values ranging from 95% to 100%, and positive predictive values of up to 34%. The highest area under the receiver operating characteristic curve was 0.88 on postoperative day 5. CONCLUSION: Procalcitonin is a useful negative test for AL following elective colorectal surgery. However, as an isolated test, it is not useful in detecting AL.

A systematic review of leadership training for medical students.

BACKGROUND: Leadership is increasingly being recognised as an essential requirement for doctors. Many medical schools are in the process of developing formal leadership training programmes, but it remains to be elucidated what characteristics make such programmes effective, and to what extent current programmes are effective, beyond merely positive learner reactions. This review's objective was to investigate the effectiveness of undergraduate medical leadership curricula and to explore common features of effective curricula. METHODS: A systematic literature search was conducted. Articles describing and evaluating undergraduate medical leadership curricula were included. Outcomes were stratified and analysed according to a modified Kirkpatrick's model for evaluating educational outcomes. RESULTS: Eleven studies met inclusion criteria. Leadership curricula evaluated were markedly heterogeneous in their duration and composition. The majority of studies utilised pre- and post- intervention questionnaires for evaluation. Two studies described randomised controlled trials with objective measures. Outcomes were broadly positive. Only one study reported neutral outcomes. CONCLUSIONS: A wide range of leadership curricula have shown subjective effectiveness, including short interventions. There is limited objective evidence however, and few studies have measured effectiveness at the system and patient levels. Further research is needed investigating objective and downstream outcomes, and use of standard frameworks for evaluation will facilitate effective comparison of initiatives.

Metronidazole following excisional haemorrhoidectomy: a systematic review and meta-analysis.

BACKGROUND: Post-operative pain is a major issue following excisional haemorrhoidectomy. Although metronidazole by both oral and topical administration routes has been shown to reduce pain after haemorrhoidectomy, its use remains a contentious issue. This systematic review and meta-analysis aims to investigate the effect of metronidazole on post-operative pain after excisional haemorrhoidectomy. METHODS: A systematic review of the literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized controlled trials (RCTs) published in PubMed/MEDLINE, EMBASE, CENTRAL and CINAHL, from inception to December 2016 were retrieved. The primary outcome investigated was post-operative pain reported as visual analogue score (VAS). Secondary outcomes were analgesia use, complications and time to return to normal activity. Meta-analysis was performed using Review Manager version 5.3 software. RESULTS: Nine randomized controlled trials including 523 patients were included in the final analysis. Five studies used oral administration and four used topical. Meta-analysis showed that post-operative VAS of patients receiving metronidazole by either route was significantly less than those in comparison groups. VAS means decreased at all the time points for both oral and topical metronidazole. Topical and oral routes of administration were not compared in any study. There was no increase in complication rates and return to normal activity was significantly earlier for patients receiving metronidazole (-4.49 days; 95% confidence interval [-7.70, -1.28]; P = 0.006). CONCLUSIONS: Both topical and oral metronidazole reduce post-operative pain without an increase in complication rates and result in an earlier return to normal activity. Further work is required to determine which the optimum route of administration is.

Intravenous lignocaine in colorectal surgery: a systematic review.

BACKGROUND: Colorectal surgery leads to morbidity during recovery including pain and fatigue. Intravenous (IV) lignocaine (IVL) has both analgesic and anti-inflammatory effects that may improve post-operative pain and recovery. The aim of this review is to compare the effectiveness of IVL to other perioperative analgesia regimens for reducing pain and opioid consumption following colorectal surgery. METHODS: Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, a literature search was conducted to identify randomized clinical trials that compared IVL with IV placebo or epidural anaesthesia in open or laparoscopic colorectal surgery. The primary outcomes were opioid requirements and pain scores assessed by visual analogue score. Data were entered into pre-designed electronic spreadsheets. RESULTS: The literature search identified 2707 studies. A total of nine randomized clinical trials met the inclusion criteria. Five studies investigated IVL compared with IV placebo and four studies investigated IVL compared with epidural anaesthesia. Two out of the five studies comparing IVL and placebo showed statistically significant reductions in opioid consumption with IVL. There was a variable degree of improvement in pain scores when IVL was compared with epidural. Two studies showed a significant difference, with lower opioid consumption and pain scores in the epidural group. Laparoscopic and open procedures could not be compared between the IVL and placebo group. CONCLUSION: IVL has shown limited benefit towards reducing early pain and morphine consumption when compared with placebo in colorectal surgery. However, IVL did not show any significant reduction in pain or opioid consumption when compared with epidural. Further research investigating IVL combined with intraperitoneal local anaesthetic is warranted.

Definition determines weight regain outcomes after sleeve gastrectomy.

BACKGROUND: Sleeve gastrectomy (SG) is one of the most commonly undertaken bariatric procedures. Weight regain after bariatric surgery, when significant, may be associated with recurrence of diabetes and deterioration in quality of life. Furthermore, it may be more common after SG than bypass procedures. Yet the understanding of the significance of weight regain is hampered by poor reporting and no consensus statements or guidelines. OBJECTIVES: To illustrate how the lack of a standard definition significantly alters reported SG outcomes and to contribute to the discussion of how weight regain should be defined. SETTING: Counties Manukau Health, a public teaching hospital that performs over 150 bariatric procedures per year. METHODS: A retrospective cohort of SG patients followed up at 5 years was used to illustrate how the presence of multiple definitions in the literature significantly affects outcome reporting for weight regain. Post hoc analyses were used to explore the relationship between weight change and clinical outcomes. RESULTS: Applying 6 definitions of weight regain to a retrospective cohort of SG patients resulted in 6 different rates ranging from 9%-91%. Post hoc analyses revealed significant associations between weight change and the Bariatric Analysis Reporting Outcome System (BAROS) score as well as patient opinion. CONCLUSION: The nonuniform reporting of weight regain appears to significantly affect SG outcome reporting. Development of consensus statements and guidelines would ameliorate this problem. Ideally, research groups with access to large robust databases would aid in the development of any proposed weight regain definitions. In the interim, bariatric literature would benefit by all published series clearly reporting how weight regain is defined in the study population.

Chewing gum and postoperative ileus in adults: a systematic literature review and meta-analysis.

INTRODUCTION: Post-operative ileus (POI) is a major problem following elective abdominal surgery. Several studies have been published investigating the use of chewing gum to reduce POI. These studies however, have produced variable results. Thus, there is currently no consensus on whether chewing gum should be widely instituted as a means to help reduce POI. METHODS: We performed a systematic literature review to evaluate whether the use of chewing gum post-operatively improves POI in abdominal surgery. A comprehensive review of the literature was conducted according to the guidelines in the PRISMA statement. The following databases were searched: MEDLINE, PUBMED, EMBASE, SCOPUS, Science Direct, CINAHL and the Cochrane Central Register of Controlled Trials. Clinical outcomes were extracted and meta-analysis was performed. RESULTS: There were 1019 patients from 12 randomised controlled studies included in this review. Only one study was conducted in an Enhanced Recovery after Surgery (ERAS) environment. Seven of the twelve studies concluded that chewing gum reduced post-operative ileus. The remaining five studies found no clinical improvement. Overall, there was a small benefit in reducing time to flatus, and time to bowel motion, but no difference in the length of stay or complications. CONCLUSION: Chewing gum offers only a small benefit in reducing time to flatus and time to passage of bowel motion following abdominal surgery. This benefit is of limited clinical significance. Further studies should be conducted in a modern peri-operative care environment.