Andrew G. Hill

Guidelines for Perioperative Care in Elective Colonic Surgery: Enhanced Recovery After Surgery (ERAS ® ) Society Recommendations

BackgroundThis review aims to present a consensus for optimal perioperative care in colonic surgery and to provide graded recommendations for items for an evidenced-based enhanced perioperative protocol.MethodsStudies were selected with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohorts. For each item of the perioperative treatment pathway, available English-language literature was examined, reviewed and graded. A consensus recommendation was reached after critical appraisal of the literature by the group.ResultsFor most of the protocol items, recommendations are based on good-quality trials or meta-analyses of good-quality trials (quality of evidence and recommendations according to the GRADE system).ConclusionsBased on the evidence available for each item of the multimodal perioperative care pathway, the Enhanced Recovery After Surgery (ERAS) Society, International Association for Surgical Metabolism and Nutrition (IASMEN) and European Society for Clinical Nutrition and Metabolism (ESPEN) present a comprehensive evidence-based consensus review of perioperative care for colonic surgery.

Guidelines for perioperative care in elective colonic surgery: Enhanced Recovery After Surgery (ERAS®) Society recommendations☆

BACKGROUND This review aims to present a consensus for optimal perioperative care in colonic surgery and to provide graded recommendations for items for an evidenced-based enhanced perioperative protocol. METHODS Studies were selected with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohorts. For each item of the perioperative treatment pathway, available English-language literature was examined, reviewed and graded. A consensus recommendation was reached after critical appraisal of the literature by the group. RESULTS For most of the protocol items, recommendations are based on good-quality trials or meta-analyses of good-quality trials (quality of evidence and recommendations according to the GRADE system). CONCLUSIONS Based on the evidence available for each item of the multimodal perioperative-care pathway, the Enhanced Recovery After Surgery (ERAS) Society, International Association for Surgical Metabolism and Nutrition (IASMEN) and European Society for Clinical Nutrition and Metabolism (ESPEN) present a comprehensive evidence-based consensus review of perioperative care for colonic surgery.

The Impact of Enhanced Recovery Protocol Compliance on Elective Colorectal Cancer Resection Results From an International Registry

BACKGROUND The ERAS (enhanced recovery after surgery) care has been shown in randomized clinical trials to improve outcome after colorectal surgery compared to traditional care. The impact of different levels of compliance and specific elements, particularly out with a trial setting, is poorly understood. OBJECTIVE This study evaluated the individual impact of specific patient factors and perioperative enhanced recovery protocol compliance on postoperative outcome after elective primary colorectal cancer resection. METHODS The international, multicenter ERAS registry data, collected between November 2008 and March 2013, was reviewed. Patient demographics, disease characteristics, and perioperative ERAS protocol compliance were assessed. Linear regression was undertaken for primary admission duration and logistic regression for the development of any postoperative complication. FINDINGS A total of 1509 colonic and 843 rectal resections were undertaken in 13 centers from 6 countries. Median length of stay for colorectal resections was 6 days, with readmissions in 216 (9.2%), complications in 948 (40%), and reoperation in 167 (7.1%) of 2352 patients. Laparoscopic surgery was associated with reduced complications [odds ratio (OR) = 0.68; P < 0.001] and length of stay (OR = 0.83, P < 0.001). Increasing ERAS compliance was correlated with fewer complications (OR = 0.69, P < 0.001) and shorter primary hospital admission (OR = 0.88, P < 0.001). Shorter hospital stay was associated with preoperative carbohydrate and fluid loading (OR = 0.89, P = 0.001), and totally intravenous anesthesia (OR = 0.86, P < 0.001); longer stay was associated with intraoperative epidural analgesia (OR = 1.07, P = 0.019). Reduced postoperative complications were associated with restrictive perioperative intravenous fluids (OR = 0.35, P < 0.001). CONCLUSIONS This analysis has demonstrated that in a large, international cohort of patients, increasing compliance with an ERAS program and the use of laparoscopic surgery independently improve outcome.

Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study

BACKGROUND Metastatic DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer has a poor prognosis after treatment with conventional chemotherapy and exhibits high levels of tumour neoantigens, tumour-infiltrating lymphocytes, and checkpoint regulators. All of these features are associated with the response to PD-1 blockade in other tumour types. Therefore, we aimed to study nivolumab, a PD-1 immune checkpoint inhibitor, in patients with dMMR/MSI-H metastatic colorectal cancer. METHODS In this ongoing, multicentre, open-label, phase 2 trial, we enrolled adults (aged ≥18 years) with histologically confirmed recurrent or metastatic colorectal cancer locally assessed as dMMR/MSI-H from 31 sites (academic centres and hospitals) in eight countries (Australia, Belgium, Canada, France, Ireland, Italy, Spain, and the USA). Eligible patients had progressed on or after, or been intolerant of, at least one previous line of treatment, including a fluoropyrimidine and oxaliplatin or irinotecan. Patients were given 3 mg/kg nivolumab every 2 weeks until disease progression, death, unacceptable toxic effects, or withdrawal from study. The primary endpoint was investigator-assessed objective response as per Response Evaluation Criteria in Solid Tumors (version 1.1). All patients who received at least one dose of study drug were included in all analyses. This trial is registered with ClinicalTrials.gov, number NCT02060188. FINDINGS Of the 74 patients who were enrolled between March 12, 2014, and March 16, 2016, 40 (54%) had received three or more previous treatments. At a median follow-up of 12·0 months (IQR 8·6-18·0), 23 (31·1%, 95% CI 20·8-42·9) of 74 patients achieved an investigator-assessed objective response and 51 (69%, 57-79) patients had disease control for 12 weeks or longer. Median duration of response was not yet reached; all responders were alive, and eight had responses lasting 12 months or longer (Kaplan-Meier 12-month estimate 86%, 95% CI 62-95). The most common grade 3 or 4 drug-related adverse events were increased concentrations of lipase (six [8%]) and amylase (two [3%]). 23 (31%) patients died during the study; none of these deaths were deemed to be treatment related by the investigator. INTERPRETATION Nivolumab provided durable responses and disease control in pre-treated patients with dMMR/MSI-H metastatic colorectal cancer, and could be a new treatment option for these patients. FUNDING Bristol-Myers Squibb.

Lymph Node Evaluation and Long-Term Survival in Stage II and Stage III Colon Cancer: A National Study

The most important prognostic factor in colonic cancer is the presence or absence of regional lymph nodes metastases. The aim of this study was to evaluate the relationship between 5-year mortality in the New Zealand population, and the number of nodes examined in Stage II and III colon cancers. New Zealand Cancer Registry data were retrieved for patients with colonic cancer from January 1995 to July 2003. Patients with incomplete entries, Stage I tumors, and distant metastases were excluded from analysis. Univariate and Cox regression models were used with 5-year mortality as the primary endpoint. The study identified 4309 patients. Younger age, female gender, Pacific Island descent, and right-sided tumors were associated with significantly higher lymph node retrieval. Cox regression analysis showed that the number of nodes examined was a significant predictor of 5-year mortality when age, sex, ethnicity, and site were controlled for. Five-year survival consistently improved between nodal strata until the 16-node mark, above which survival advantage was minimal. For Stage III cancers, a higher lymph node ratio was associated with a significant increase in mortality. Increased rates of nodal examination are associated with a significantly lower 5-year mortality for Stage II and III colonic cancer, but this survival advantage appears to be minimal after the 16-node mark. The lymph node ratio has been validated as a powerful predictor of survival in Stage III cancer. Our results support the current practice of harvesting and examining as many nodes as possible during attempted curative resection.BackgroundThe most important prognostic factor in colonic cancer is the presence or absence of regional lymph nodes metastases. The aim of this study was to evaluate the relationship between 5-year mortality in the New Zealand population, and the number of nodes examined in Stage II and III colon cancers.MethodsNew Zealand Cancer Registry data were retrieved for patients with colonic cancer from January 1995 to July 2003. Patients with incomplete entries, Stage I tumors, and distant metastases were excluded from analysis. Univariate and Cox regression models were used with 5-year mortality as the primary endpoint.ResultsThe study identified 4309 patients. Younger age, female gender, Pacific Island descent, and right-sided tumors were associated with significantly higher lymph node retrieval. Cox regression analysis showed that the number of nodes examined was a significant predictor of 5-year mortality when age, sex, ethnicity, and site were controlled for. Five-year survival consistently improved between nodal strata until the 16-node mark, above which survival advantage was minimal. For Stage III cancers, a higher lymph node ratio was associated with a significant increase in mortality.ConclusionsIncreased rates of nodal examination are associated with a significantly lower 5-year mortality for Stage II and III colonic cancer, but this survival advantage appears to be minimal after the 16-node mark. The lymph node ratio has been validated as a powerful predictor of survival in Stage III cancer. Our results support the current practice of harvesting and examining as many nodes as possible during attempted curative resection.

Systematic review and meta-analysis of use of serum C-reactive protein levels to predict anastomotic leak after colorectal surgery.

Several recent studies have investigated the role of C‐reactive protein (CRP) as an early marker of anastomotic leakage following colorectal surgery. The aim of this systematic review and meta‐analysis was to evaluate the predictive value of CRP in this setting.

Randomized clinical trial of enhanced recovery versus standard care after laparoscopic sleeve gastrectomy.

Optimized perioperative care within an enhanced recovery after surgery (ERAS) protocol is designed to reduce morbidity after surgery, resulting in a shorter hospital stay. The present study evaluated this approach in the context of sleeve gastrectomy for patients with morbid obesity.

Medical students-as-teachers: a systematic review of peer-assisted teaching during medical school

Introduction International interest in peer-teaching and peer-assisted learning (PAL) during undergraduate medical programs has grown in recent years, reflected both in literature and in practice. There, remains however, a distinct lack of objective clarity and consensus on the true effectiveness of peer-teaching and its short- and long-term impacts on learning outcomes and clinical practice. Objective To summarize and critically appraise evidence presented on peer-teaching effectiveness and its impact on objective learning outcomes of medical students. Method A literature search was conducted in four electronic databases. Titles and abstracts were screened and selection was based on strict eligibility criteria after examining full-texts. Two reviewers used a standard review and analysis framework to independently extract data from each study. Discrepancies in opinions were resolved by discussion in consultation with other reviewers. Adapted models of “Kirkpatrick’s Levels of Learning” were used to grade the impact size of study outcomes. Results From 127 potential titles, 41 were obtained as full-texts, and 19 selected after close examination and group deliberation. Fifteen studies focused on student-learner outcomes and four on student-teacher learning outcomes. Ten studies utilized randomized allocation and the majority of study participants were self-selected volunteers. Written examinations and observed clinical evaluations were common study outcome assessments. Eleven studies provided student-teachers with formal teacher training. Overall, results suggest that peer-teaching, in highly selective contexts, achieves short-term learner outcomes that are comparable with those produced by faculty-based teaching. Furthermore, peer-teaching has beneficial effects on student-teacher learning outcomes. Conclusions Peer-teaching in undergraduate medical programs is comparable to conventional teaching when utilized in selected contexts. There is evidence to suggest that participating student-teachers benefit academically and professionally. Long-term effects of peer-teaching during medical school remain poorly understood and future research should aim to address this.

A systematic review of resident-as-teacher programmes

Context  Residents in all disciplines serve as clinical teachers for medical students. Since the 1970s, there has been increasing evidence to demonstrate that residents wish to teach and that they respond positively to formal teacher training. Effective resident‐as‐teacher (RaT) programmes have resulted in improved resident teaching skills. Current evidence, however, is not clear about the specific features of an effective RaT programme.

Implementation of ERAS and how to overcome the barriers

BACKGROUND Multimodal care or Enhanced Recovery after Surgery (ERAS) protocols are gaining popularity in order to modify surgical stress responses after colonic resection. However, these protocols are not straightforward to implement as peri-operative care is varied. We aimed to identify areas that may need attention in order to successfully change practice. METHOD The literature was reviewed for current practice, methods and issues in implementing ERAS. Based on this and our own experience we discuss several important areas that need particular attention in developing and sustaining an ERAS program. RESULTS International surveys have shown that current peri-operative care in colorectal resection is not evidence based. Important aspects of the ERAS philosophy including patient counselling, teamwork and attitude change are identified and discussed. CONCLUSION Implementing evidence-based peri-operative care into practice is challenging. Barriers to multimodal recovery pathways should be addressed.