Metabolic Phenotyping and Systems Biology in Surgery
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Sepsis
研究概览
简要总结
This work will use a new approach to measure how surgery effects human biochemistry and metabolism. It will create a metabolic signature or 'phenotype' for surgical injury that will help clinicians choose the right surgical treatments for an individual. This is because metabolism is based on an individual's genes, disease burden and environmental influences such as gut microbiota. This study will use a scientific method based on computational analysis of spectra taken from techniques known as Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR) spectroscopy. This science is called 'metabonomics' and it has many advantages. Firstly, it provides a measure of thousands of metabolites at a single moment in time that are unique to the individual and it therefore gives a 'systems' overview of a persons metabolism. Secondly it is able to process many hundreds of samples quickly. The investigators are aiming to integrate the investigators metabolic data with genetic information about patients or bacteria wherever possible. This will be the first time that a 'systems biology' approach has been used in surgery, with potentially significant gains to me made in pre operative risk stratification and optimisation. By performing this analysis at all stages of the surgical journey (preoperatively, during the operation and after the surgery) it will ensure the right treatments are given to the right patient at the right time. By creating longitudinal models of the biochemical responses to surgery, predict at a much earlier stage those patients at risk of developing complications. This will improve outcome after surgery. This work will use a metabonomic approach to create new tools for surgeons to use during operations based on tissue biology. For example the investigators will be able to measure the metabolic content of tumours in real time by measuring the biological content of diathermy smoke. This has the potential to change intra-operative decision making and further improve outcome.
详细描述
A systems perspective can improve surgical decision making both before and after surgery in real time. Specifically, we hypothesize that it may provide diagnostic and prognostic information of importance that is more accurate than current biochemical approaches. This is because it accounts for important environmental influences on surgical outcome such as pharmacotherapy and the gut microbiota.
The secondary hypothesis is that this approach can provide real time molecular feedback to the operator during surgery about tissue type and pathology.
This work will therefore need to study patients having surgery under a range of different conditions and states, and by varying types of surgical intervention. It is known that patients with cancer for example have quite different metabolic requirements to those without. This has significant implications for the development of personalized management strategies for patients with cancer undergoing surgery. It is essential that this study definitively proves that the technology is able to make a description between patients with significantly different disease states and also that it can differentiate this from the type and magnitude of the surgical procedure being performed and the timing of the surgery. Therefore, this work will involve a heterogeneous patient cohort.
Study design:
This study will be subject to research governance structures provided internally within the department of Biosurgery and Surgical technology in conjunction with the section of Biomolecular medicine for the safe use of samples and machinery. It will also possess a clinical steering committee to assess the progress, clinical outcomes, safety and timely completion of the work.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Elective surgery (n=200)
- •Patients with cancer. This will include patients with malignancy of the gastrointestinal and colorectal tract (including those excised by microsurgery)cancer of the breast or solid tumours of the kidney.
- •Patients with benign disease of the bowel requiring surgery e.g. inflammatory bowel disease
- •Benign surgical conditions, usually operated on in a day surgery setting. These will specifically be of the biliary tree (gall stones) and the anterior abdominal wall (e.g. Hernia surgery)
- •Patients will be recruited if seen under the 'two week' wait rule with suspected cancer for the general surgery, upper GI surgery, Breast and Urology surgery teams at St. Mary's hospital in the outpatient setting will be recruited
- •Patients attending for elective inpatient surgery under the general, upper GI or breast surgery teams at St. Mary's hospital, London will be recruited at the pre admission clinic.
- •Acute surgery (n=200) Patients presenting to Accident and emergency under the care of the general surgery on call team will be recruited into this study group. This study group will have the following subgroups:
- •Acute abdominal pain
- •Patients with acute sepsis thought to be of surgical origin as diagnosed by their history, clinical examination and routine investigations.
- •Patients suffering major trauma with an Injury severity score (ISS) of >15, multiple injuries, who require surgery or who have >1 organ system that is failed or who are admitted to the intensive care department.
排除标准
- •All patients under the age of 18 years
- •All patients who are pregnant
- •Patients receiving Advanced Life Support by cardiopulmonary resuscitation on their arrival in hospital.
- •Patients with advanced cancer only suitable for palliative care at presentation to the clinical team.
- •Patients presenting for the first time with other known malignancies for which they are receiving treatment e.g. Prostate cancer
- •Patients already recruited into other clinical studies.
结局指标
主要结局
Sepsis
时间窗: 30 days
Daily sampling of patients during the post operative period to determine early biomarkers for the development of sepsis
次要结局
- Local and distant recurrence(5 years)
- Organ failure(30 days)
- Oncological resection margins(10 days)
- Mortality(30 days)