The causes of constipation. Reclassifying constipation using MRI and high resolution manometry to define mechanism of disease and target treatment.

便秘的原因。

• 批准号: MR/N026810/1
• 负责人: Robin Spiller
• 金额: $ 160.04万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN026810%2F1
• 关键词: causes; constipation.; Reclassifying; constipation; using

Constipation is a common problem affecting up to 1 in 7 of the population but treatment is unsatisfactory for over half the patients treated. One reason may be that the current system of classification which determines doctors' choice of treatment is based on symptoms rather than underlying causes. This is because defining the causes, which include abnormal contractions within the large bowel, is difficult at present as this can only be done by emptying the colon and measuring contraction pressure with small probes (a technique called manometry) within the bowel. This is time consuming, technically difficult and requires highly specialist staff to perform. Also, it requires a camera test (colonoscopy) to actually put the probe in the right place. This is expensive and unpleasant for patients. The traditional theory of constipation is that it is due to underactivity of the colon i.e. reduced or absent contractions. We have recently developed a new magnetic resonance imaging (MRI) technique, which is non-invasive (does not involve putting anything up the bowel), acceptable to patients and potentially more widely available as it can be performed using standard MRI scanners. We have applied this MRI method to a group of patients with constipation. Surprisingly some patients have normal or increased numbers of bowel contractions (motility) in the right half of the colon where the small intestinal contents enter the colon. We see this in around half our patients despite finding slow movement throughout the colon (called slow transit). Recently advances in directly measuring pressure using manometry have shown that colonic contractions in patients with constipation-type irritable bowel syndrome may be uncoordinated or may actually serve to propel fluid backwards (retrograde contractions) rather than forwards as one would normally expect. An increase in such contractions would impede movement through the bowel (prolonging transit time) and by separating fluid from solid make the stool harder. This is a new and radically different view of the cause of constipation.At 3 leading University Hospitals in Nottingham and London we propose to study up to 80 patients with constipation and 40 healthy volunteers, using MRI and manometry to determine if our new MRI methods can be used to detect abnormal contractions as well as manometry can. Our first aim is to confirm our original findings. We will also compare motility in both the right and left side of the colon using MRI to see if activity is similar on the two sides. We will also assess the motility of the left colon using a new highly sensitive manometry technique to see if classifying patients in this way identifies the same patients as the MRI test. We will then invite subjects who have had their colonic contractions assessed to take part in a trial of two very different treatments given in random order, one which increases contractions (called a prokinetic) and one which reduces contractions (muscle relaxant). During the trial neither the subject nor investigator will know which treatment has been given. We want to know if our new motility test will predict which treatment works to reduce symptoms (constipation and pain). We hypothesise that giving a prokinetic to patients with normal or increased contractions will aggravate symptoms but improve symptoms in those with underactive contractions. Conversely giving a muscle relaxant to reduce contractions will improve those with increased or abnormal contractions but not help those with normal or underactive contractions. If successful we hope that future treatment of constipation unresponsive to simple measures will be based on objective assessment using the new MRI test rather than the current unsatisfactory symptom-based methods. This should substantially increase the proportion of patients who are satisfied with their treatment, thereby reducing doctor visits, investigations and time off work.

便秘是一种常见的问题，影响到高达七分之一的人口，但治疗对一半以上的患者来说并不令人满意。一个原因可能是，目前决定医生治疗选择的分类系统是基于症状而不是潜在原因。这是因为目前很难确定病因，包括大肠内的异常收缩，因为这只能通过排空结肠并在肠道内用小探头测量收缩压力(一种称为测压技术)来完成。这既耗费时间，又有技术难度，而且需要高度专业的工作人员来执行。此外，它还需要进行摄像测试(结肠镜检查)，才能真正将探头放在正确的位置。这对患者来说既昂贵又令人不快。传统的便秘理论认为便秘是由于结肠活动不足，即收缩减少或消失所致。我们最近开发了一种新的磁共振成像(MRI)技术，这种技术是非侵入性的(不涉及将任何东西放入肠道)，患者可以接受，而且可能会更广泛地使用，因为它可以使用标准的MRI扫描仪进行。我们已经将这种MRI方法应用于一组便秘患者。令人惊讶的是，一些患者在进入结肠的右半结肠有正常或增加的肠收缩(运动)。我们在大约一半的患者中发现了这种情况，尽管在整个结肠中发现了缓慢的运动(称为慢传输)。最近，使用测压技术直接测量压力的进展表明，便秘型肠易激综合征患者的结肠收缩可能是不协调的，或者实际上可能是推动液体向后(逆行收缩)，而不是人们通常预期的向前推进。这种收缩的增加会阻碍通过肠道的运动(延长通过时间)，并通过将液体和固体分离而使粪便变得更硬。这是对便秘病因的一种新的、完全不同的观点。在诺丁汉和伦敦的三家领先的大学医院，我们提议研究多达80名便秘患者和40名健康志愿者，使用MRI和测压来确定我们的新MRI方法是否可以像测压一样用于检测异常收缩。我们的首要目标是确认我们最初的发现。我们还将使用核磁共振技术比较左右两侧结肠的活动情况，看看两侧的活动是否相似。我们还将使用一种新的高灵敏度测压技术来评估左半结肠的运动性，看看以这种方式对患者进行分类是否能识别出与MRI测试相同的患者。然后，我们将邀请接受了结肠收缩评估的受试者参加两种完全不同的治疗方法的试验，一种是增加收缩(称为促动力疗法)，另一种是减少收缩(肌肉松弛药)。在审判期间，无论是受试者还是调查人员都不知道进行了哪种治疗。我们想知道我们的新运动测试是否能预测哪种治疗方法能有效地减轻症状(便秘和疼痛)。我们假设，给宫缩正常或增加的患者服用促动力药会加重症状，但对宫缩不活跃的患者会改善症状。相反，给予肌肉松弛药来减少宫缩将改善那些宫缩增加或异常的人，但对那些正常或不活跃的宫缩没有帮助。如果成功，我们希望未来对简单措施无效的便秘的治疗将基于使用新的MRI测试的客观评估，而不是目前不满意的基于症状的方法。这将大大增加患者对自己的治疗满意的比例，从而减少就诊、检查和休假时间。

项目成果

Insights Into the Different Effects of Food on Intestinal Secretion Using Magnetic Resonance Imaging.

使用磁共振成像深入了解食物对肠道分泌的不同影响。

• DOI: 10.1002/jpen.1157
• 发表时间: 2018
• 期刊: JPEN. Journal of parenteral and enteral nutrition
• 作者: Wilkinson-Smith VC

O52 Reclassifying constipation using colonic volume assessed by MRI, whole gut transit, psychological distress and pain scores

O52 使用 MRI 评估的结肠体积、全肠道传输、心理困扰和疼痛评分对便秘进行重新分类

• DOI: 10.1136/gutjnl-2023-bsg.51
• 发表时间: 2023
• 作者: Wilkinson-Smith V

O59 MRI methods to define colonic function in health and constipation

O59 MRI 方法定义健康和便秘中的结肠功能

• DOI: 10.1136/gutjnl-2020-bsgcampus.59
• 发表时间: 2021
• 作者: Wilkinson-Smith V

The MRI colonic function test: Reproducibility of the Macrogol stimulus challenge.

MRI 结肠功能测试：聚乙二醇刺激挑战的重现性。

• DOI: 10.1111/nmo.13942
• 发表时间: 2020
• 期刊: Neurogastroenterology and motility
• 影响因子: 3.5
• 作者: Wilkinson-Smith V

Tu1971 - Assessment of Colonic Motility Using Magnetic Resonance Imaging: Reproducibility of a Macrogol Challenge

Tu1971 - 使用磁共振成像评估结肠运动：聚乙二醇挑战的重现性

• DOI: 10.1016/s0016-5085(18)33574-1
• 发表时间: 2018
• 期刊: Gastroenterology
• 影响因子: 29.4
• 作者: Wilkinson-Smith V