Andrew G. Hill

Bio: Andrew G. Hill is an academic researcher from University of Auckland. The author has contributed to research in topics: Randomized controlled trial & Colectomy. The author has an hindex of 54, co-authored 385 publications receiving 13064 citations. Previous affiliations of Andrew G. Hill include Auckland City Hospital & Brigham and Women's Hospital.

Guidelines for perioperative care in elective colonic surgery: Enhanced recovery after surgery (ERAS®) society recommendations

Abstract: This is the fourth updated Enhanced Recovery After Surgery (ERAS®) Society guideline presenting a consensus for optimal perioperative care in colorectal surgery and providing graded recommendations for each ERAS item within the ERAS® protocol. A wide database search on English literature publications was performed. Studies on each item within the protocol were selected with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohorts and examined, reviewed and graded according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. All recommendations on ERAS® protocol items are based on best available evidence; good-quality trials; meta-analyses of good-quality trials; or large cohort studies. The level of evidence for the use of each item is presented accordingly. The evidence base and recommendation for items within the multimodal perioperative care pathway are presented by the ERAS® Society in this comprehensive consensus review.

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

Abstract: Summary 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.

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

Abstract: 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.

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

Abstract: 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.

Medscape

Abstract: Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

Abstract: The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor–1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair–deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair–deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers’ tissue of origin.

TGF-beta signaling and the fibrotic response.

Abstract: The cause of fibrotic diseases, pathologies characterized by excessive production, deposition, and contraction of extracellular matrix, is unknown. To understand the molecular basis of fibrotic disease, it is essential to appreciate how matrix deposition is normally controlled and how this process is dysregulated in fibrogenesis. This review discusses the current state of knowledge concerning interactions among the profibrotic proteins transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF, CCN2), and ED-A fibronectin (ED-A FN) and the antifibrotic proteins tumor necrosis factor-α (TNF-α) and γ-interferon (IFN-γ).—Leask, A., Abraham, D. J. TGF-β signaling and the fibrotic response.

Enhanced Recovery After Surgery: A Review

Abstract: Importance Enhanced Recovery After Surgery (ERAS) is a paradigm shift in perioperative care, resulting in substantial improvements in clinical outcomes and cost savings. Observations Enhanced Recovery After Surgery is a multimodal, multidisciplinary approach to the care of the surgical patient. Enhanced Recovery After Surgery process implementation involves a team consisting of surgeons, anesthetists, an ERAS coordinator (often a nurse or a physician assistant), and staff from units that care for the surgical patient. The care protocol is based on published evidence. The ERAS Society, an international nonprofit professional society that promotes, develops, and implements ERAS programs, publishes updated guidelines for many operations, such as evidence-based modern care changes from overnight fasting to carbohydrate drinks 2 hours before surgery, minimally invasive approaches instead of large incisions, management of fluids to seek balance rather than large volumes of intravenous fluids, avoidance of or early removal of drains and tubes, early mobilization, and serving of drinks and food the day of the operation. Enhanced Recovery After Surgery protocols have resulted in shorter length of hospital stay by 30% to 50% and similar reductions in complications, while readmissions and costs are reduced. The elements of the protocol reduce the stress of the operation to retain anabolic homeostasis. The ERAS Society conducts structured implementation programs that are currently in use in more than 20 countries. Local ERAS teams from hospitals are trained to implement ERAS processes. Audit of process compliance and patient outcomes are important features. Enhanced Recovery After Surgery started mainly with colorectal surgery but has been shown to improve outcomes in almost all major surgical specialties. Conclusions and Relevance Enhanced Recovery After Surgery is an evidence-based care improvement process for surgical patients. Implementation of ERAS programs results in major improvements in clinical outcomes and cost, making ERAS an important example of value-based care applied to surgery.