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Dinning PG. An expert's guide to classical manometric patterns seen in high-resolution colonic manometry. Expert Rev Gastroenterol Hepatol 2025:1-14. [PMID: 39953914 DOI: 10.1080/17474124.2025.2468301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 01/30/2025] [Accepted: 02/13/2025] [Indexed: 02/17/2025]
Abstract
INTRODUCTION High-resolution colonic manometry is a research and diagnostic tool used to evaluate colonic motility. Used in health it helps us understand normal colonic motility and the colonic response to physiological stimuli such as meal, as well as chemical (laxatives) and mechanical (distension) stimuli. In pediatric and adult patients with suspected colonic disorders, it can help to understand the abnormal colonic motility associated with the condition. AREA COVERED High-resolution manometric catheters contain multiple closely spaced sensors that detect intraluminal pressure changes and contractile force, which can be interpreted as contractile activity. This activity forms several distinctive motor patterns that help in understanding normal colonic physiology and provide insights into the potential pathophysiology underlying colonic disorders such as constipation. After a PubMed search of colonic high-resolution manometry studies, this review provides an overview of the characterized motor patterns, when they occur, how they are initiated, their clinical relevance, and their role, if any, in guiding therapeutic interventions. EXPERT OPINION High-resolution colonic manometry has identified motor patterns that were missed or mislabeled by low-resolution recordings. How best to use this information to guide treatment remains to be determined.
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Affiliation(s)
- Phil G Dinning
- Department of Gastroenterology, Flinders Medical Centre, Beford Park, SA
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Hui JCM, Du P, Webb SE, Liu JYH, Ngan MP, Lu Z, Ng HSH, Yang L, Khalid A, Liu L, Li Z, Deng Y, Cui D, Rudd JA. Imaging analytical technique to assess gastrointestinal motility in vivo using zebrafish larvae with diabetes mellitus-like traits. PLoS One 2024; 19:e0314515. [PMID: 39621609 PMCID: PMC11611181 DOI: 10.1371/journal.pone.0314515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Accepted: 11/11/2024] [Indexed: 01/04/2025] Open
Abstract
In diabetes mellitus (DM), the prevalence of gastrointestinal (GI) complications, including constipation, diarrhoea, gastroparesis, and/or enteropathy, can be up to ~75%. In this study, we compared three zebrafish larvae models of DM and established an analytical protocol for GI motility. Larvae were fed with either a standard diet (SD; control), or one of three diets to induce a DM-like phenotype: excessive feeding of SD food (ED), a high-fat diet (HFD), or exposing SD-fed larvae to 30 mmol/L glucose (SDG). DM was confirmed using a body-mass index, assessment of adipose deposit areas, two glucose assays, and one insulin assay. An analytical technique, whereby GI motility was quantified using pixel differences to track displacement along the centreline of the anterior, middle, and posterior intestine (AI, MI, and PI, respectively), was developed. Our results indicated that clear DM-like traits were observed in the HFD and SGD models, but not the ED model. In the SD controls, the AI showed similar anterograde and retrograde contractions indicating normal GI mixing; the MI exhibited more prominent forward contractions, and the PI showed distinct rectal waves. Compared to the SD, the HFD and SDG models exhibited significantly increased and decreased contraction velocities and could be used as models of diarrhoea and constipation in DM, respectively, while the ED model showed comparatively little change in motility. Together, these data indicate that complex changes in GI motility are associated with diet and therapeutics used to alleviate GI complications in DM should take these into account. Ultimately, the HFD and SDG models can be used to investigate different aspects of GI motility in association to DM. Hence, zebrafish are a useful model for studying GI dysfunctions due to DM and/or DM medication side-effects.
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Affiliation(s)
- Jessica C. M. Hui
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Peng Du
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
| | - Sarah E. Webb
- Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong SAR, China
| | - Julia Y. H. Liu
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Man Piu Ngan
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Zengbing Lu
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Heidi S. H. Ng
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Lingqing Yang
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Aleena Khalid
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Luping Liu
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Zitong Li
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yingyi Deng
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Dexuan Cui
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - John A. Rudd
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
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Hua F, Yan G, Wang L, Wu T. Study on Intestinal Pressure after Implantation of Biaxial Actuated Artificial Anal Sphincter in Animal. Biomed Microdevices 2024; 26:38. [PMID: 39215802 DOI: 10.1007/s10544-024-00722-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/27/2024] [Indexed: 09/04/2024]
Abstract
Fecal incontinence (FI) referred to the inability to control the leakage of solid, liquid, or gaseous feces, the artificial anal sphincter (AAS) was the last resort for patients with FI except enterostomy. In order to the clinical application value of AAS was improved, the detection and analysis of intestinal pressure information was very necessary. Biaxial actuated artificial anal sphincter (BAAS) was a new type of AAS, which not only had a stable, long-term and safe energy supply, but also could provide real-time feedback of intestinal pressure information. In this paper, the BAAS was implanted into piglets for a long-term animal experiment. Piglets' life habits, defecation habits and intestinal pressure were analyzed. The analysis results showed that the BAAS system had good feces control effect, when the actuator of the BAAS system was closed, there was basically no fecal leakage of piglets, and when the actuator of the BAAS system was opened, the piglets could defecate normally. Under the normal condition of the piglets' health state and the BAAS's operating state, the accuracy of the defecation perception reached to 65.79%. This study realized the in-depth study of the mechanism of piglets' defecation, and provided guidance for the development of a new generation of AAS.
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Affiliation(s)
- Fangfang Hua
- School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Guozheng Yan
- School of Biomedical Engineering, Shanghai Jiao Tong University, Minhang District, 800 Dongchuan Road, Shanghai, 200240, China.
| | - Lichao Wang
- School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Tong Wu
- School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China
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Taclob JA, Kalas MA, McCallum RW. Examining linaclotide for the treatment of chronic idiopathic constipation. Expert Opin Pharmacother 2024; 25:1281-1290. [PMID: 39058326 DOI: 10.1080/14656566.2024.2386160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 07/18/2024] [Accepted: 07/25/2024] [Indexed: 07/28/2024]
Abstract
INTRODUCTION Chronic idiopathic constipation (CIC) is characterized by infrequent bowel movements and hard stools lasting for at least three months or longer. This disease affects 8-12% of the US population and 10-17% of the world population. Treatment and management involve identifying the primary cause, changing dietary habits, and adequate physical activity. Linaclotide is a guanylate cyclase-agonist acting locally in the luminal surface of the intestinal enterocyte leading to a signal transduction cascade, activation of the cystic fibrosis transmembrane conductance regulator (CFTR), thus increasing secretion of chloride and bicarbonate into the intestinal lumen with eventual increased intestinal fluid and faster transit time. AREAS COVERED We reviewed multiple studies and did a thorough literature review on CIC including its pathophysiology. Through this literature review, we were able to discuss and give the context and rationale for drug regimens indicated for CIC. EXPERT OPINION The era we live in right now is akin to nutrient-rich and fertilized soil as knowledge and resources are abundant. The opportunities and potential are endless. Constipation being more extensively studied, our understanding of medications and diseases broadens, leading to novel medications being discovered. Linaclotide is a pioneer in this aspect and can pave the way for future generations.
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Affiliation(s)
- Jeff Angelo Taclob
- Department of Internal Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
| | - M Ammar Kalas
- Division of Gastroenterology, Department of Internal Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
| | - Richard W McCallum
- Division of Gastroenterology, Department of Internal Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
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Wattchow DA, Brookes SJ, Spencer NJ, Heitmann PT, De Giorgio R, Costa M, Dinning PG. From the organ bath to the whole person: a review of human colonic motility. ANZ J Surg 2024; 94:320-326. [PMID: 37974532 DOI: 10.1111/ans.18779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 11/01/2023] [Accepted: 11/02/2023] [Indexed: 11/19/2023]
Abstract
Motor function of the colon is essential for health. Our current understanding of the mechanisms that underlie colonic motility are based upon a range of experimental techniques, including molecular biology, single cell studies, recordings from muscle strips, analysis of part or whole organ ex vivo through to in vivo human recordings. For the surgeon involved in the clinical management of colonic conditions this amounts to a formidable volume of material. Here, we synthesize the key findings from these various experimental approaches so that surgeons can be better armed to deal with the complexities of the colon.
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Affiliation(s)
- David A Wattchow
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
- Departments of Surgery and Gastroenterology, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Simon J Brookes
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Nick J Spencer
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Paul T Heitmann
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Roberto De Giorgio
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Marcello Costa
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Phil G Dinning
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
- Departments of Surgery and Gastroenterology, Flinders Medical Centre, Adelaide, South Australia, Australia
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Seo SHB, Wells CI, Dickson T, Rowbotham D, Gharibans A, Calder S, Bissett I, O'Grady G, Erickson JC. Validation of body surface colonic mapping (BSCM) against high resolution colonic manometry for evaluation of colonic motility. Sci Rep 2024; 14:4842. [PMID: 38418514 PMCID: PMC10902299 DOI: 10.1038/s41598-024-54429-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 02/13/2024] [Indexed: 03/01/2024] Open
Abstract
Abnormal cyclic motor pattern (CMP) activity is implicated in colonic dysfunction, but the only tool to evaluate CMP activity, high-resolution colonic manometry (HRCM), remains expensive and not widely accessible. This study aimed to validate body surface colonic mapping (BSCM) through direct correlation with HRCM. Synchronous meal-test recordings were performed in asymptomatic participants with intact colons. A signal processing method for BSCM was developed to detect CMPs. Quantitative temporal analysis was performed comparing the meal responses and motility indices (MI). Spatial heat maps were also compared. Post-study questionnaires evaluated participants' preference and comfort/distress experienced from either test. 11 participants were recruited and 7 had successful synchronous recordings (5 females/2 males; median age: 50 years [range 38-63]). The best-correlating MI temporal analyses achieved a high degree of agreement (median Pearson correlation coefficient (Rp) value: 0.69; range 0.47-0.77). HRCM and BSCM meal response start and end times (Rp = 0.998 and 0.83; both p < 0.05) and durations (Rp = 0.85; p = 0.03) were similar. Heat maps demonstrated good spatial agreement. BSCM is the first non-invasive method to be validated by demonstrating a direct spatio-temporal correlation to manometry in evaluating colonic motility.
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Affiliation(s)
- Sean H B Seo
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Cameron I Wells
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Department of Surgery, Auckland District Health Board, Auckland, New Zealand
| | - Tully Dickson
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - David Rowbotham
- Department of Gastroenterology, Auckland City Hospital, Te Whatu Ora Health New Zealand, Auckland, New Zealand
| | - Armen Gharibans
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
| | - Stefan Calder
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
| | - Ian Bissett
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Department of Surgery, Auckland District Health Board, Auckland, New Zealand
| | - Greg O'Grady
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Jonathan C Erickson
- Alimetry Ltd, Auckland, New Zealand.
- Department of Physics and Engineering, Washington and Lee University, Lexington, USA.
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Meng LH, Mo XW, Yang BY, Qin HQ, Song QZ, He XX, Li Q, Wang Z, Mo CL, Yang GH. To explore the pathogenesis of anterior resection syndrome by magnetic resonance imaging rectal defecography. World J Gastrointest Surg 2024; 16:529-538. [PMID: 38463367 PMCID: PMC10921216 DOI: 10.4240/wjgs.v16.i2.529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 11/26/2023] [Accepted: 01/29/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND Over 90% of rectal cancer patients develop low anterior resection syndrome (LARS) after sphincter-preserving resection. The current globally recognized evaluation method has many drawbacks and its subjectivity is too strong, which hinders the research and treatment of LARS. AIM To evaluate the anorectal function after colorectal cancer surgery by quantifying the index of magnetic resonance imaging (MRI) defecography, and pathogenesis of LARS. METHODS We evaluated 34 patients using the standard LARS score, and a new LARS evaluation index was established using the dynamic images of MRI defecography to verify the LARS score. RESULTS In the LARS score model, there were 10 (29.41%) mild and 24 (70.58%) severe cases of LARS. The comparison of defecation rate between the two groups was 29.36 ± 14.17% versus 46.83 ± 18.62% (P = 0.004); and MRI-rectal compliance (MRI-RC) score was 3.63 ± 1.96 versus 7.0 ± 3.21 (P = 0.001). Severe and mild LARS had significant differences using the two evaluation methods. There was a significant negative correlation between LARS and MRI-RC score (P < 0.001), and they had a negative correlation with defecation rate (P = 0.028). CONCLUSION MRI defecography and standard LARS score can both be used as an evaluation index to study the pathogenesis of LARS.
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Affiliation(s)
- Ling-Hou Meng
- Department of Gastrointestinal Surgery, Guangxi Clinical Research Center for Colorectal Cancer, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xian-Wei Mo
- Department of Colorectal and Anal Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Bing-Yu Yang
- Department of Gastrointestinal Surgery, Guangxi Clinical Research Center for Colorectal Cancer, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Hai-Quan Qin
- Department of Gastrointestinal Surgery, Guangxi Clinical Research Center for Colorectal Cancer, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Qing-Zhou Song
- Department of Gastrointestinal Surgery, Guangxi Clinical Research Center for Colorectal Cancer, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xin-Xin He
- Department of Gastrointestinal Surgery, Guangxi Clinical Research Center for Colorectal Cancer, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Qiang Li
- Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Zheng Wang
- Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Chang-Lin Mo
- Department of Gastrointestinal Surgery, Guangxi Clinical Research Center for Colorectal Cancer, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guo-Hai Yang
- First Department of Chemotherapy, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Yuan Y, Lu Y, Zhang Z, Cheng W, Yan K, Zheng Y, Jin Y, Liu Z. Characteristics of the Cajal interstitial cells and intestinal microbiota in children with refractory constipation. Microb Pathog 2023; 184:106373. [PMID: 37769855 DOI: 10.1016/j.micpath.2023.106373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 09/21/2023] [Accepted: 09/22/2023] [Indexed: 10/03/2023]
Abstract
BACKGROUND Children with refractory constipation experience intense and persistent symptoms that greatly diminish their quality of life. However, the underlying pathophysiological mechanism responsible for this condition remains uncertain. Our objective was to evaluate characteristics of colonic motor patterns and interstitial cells of Cajal (ICCs) to refractory constipation children, as well as intestinal microbiota compositions. METHODS Colonic manometry (CM) was conducted on a cohort of 30 patients with refractory constipation to assess colonic motility, and 7 of them underwent full-thickness colon biopsy specimens. Another 5 colonic specimens from nonconstipation patients were collected to identify the ICCs by immunohistochemistry. Fecal samples from 14 children diagnosed with refractory constipation and subjecting 28 age-matched healthy children to analysis using high-throughput sequencing of 16S rRNA. RESULTS According to CM results, dividing 30 children with refractory constipation into 2 groups: normal group (n = 10) and dysmotility group (n = 20). Dysmotility subjects showed lower colonic motility. Antegrade propagating pressure waves, retrograde propagating pressure waves, and periodic colonic motor activity were common in normal subjects and rare in dysmotility subjects (32.7 ± 8.9 vs 20.7 ± 13.0/17 h, P < 0.05, 11.5 ± 2.3 vs 9.6 ± 2.3/17 h, P < 0.05, and 5.2 ± 8.9 vs 3.5 ± 6.8 cpm, P < 0.005, respectively), whereas periodic rectal motor activity was more common in dysmotility subjects (3.4 ± 4.8 vs 3.0 ± 3.1 cpm, P < 0.05). Dysmotility subjects exhibited a significantly greater number of preprandial simultaneous pressure waves compared to the normal subjects (32.3 ± 25.0 vs 23.6 ± 13.2/1 h, P < 0.005). Dysmotility subjects displayed a notable decrease in postprandial count of antegrade propagating pressure waves and high amplitude propagating pressure waves when compared to normal subjects (3.9 ± 2.9 vs 6.9 ± 3.5/1 h and 2.3 ± 1.5 vs 5.4 ± 2.9/1 h, respectively, P < 0.05). The number, distribution, and morphology of ICCs were markedly altered in refractory constipation compared children to the controls (P < 0.05). Children diagnosed with refractory constipation displayed a distinct dissimilarity in composition of their intestinal microbiota comparing with control group (P < 0.005). In genus level, Bacteroidetes represented 34.34% and 43.78% in the refractory constipation and control groups, respectively. Faecalibacterium accounted for 3.35% and 12.56%, respectively (P < 0.005). Furthermore, the relative abundances of Faecalibacterium (P < 0.005), Lachnospira (P < 0.05), and Haemophilus (P < 0.05) significantly decreased, whereas those of Parabacteroides (P < 0.05), Alistipes (P < 0.005), Prevotella_2 (P < 0.005), [Ruminococcus]_torques_group (P < 0.005), Barnesiella (P < 0.05), Ruminococcaceae_UCG-002 (P < 0.005), and Christensensenellaceae_R-7_group (P < 0.05) were markedly increased in children with refractory constipation. CONCLUSIONS Dysmotility subjects showed lower colonic motility and an impaired postprandial colonic response. The decreased number and abnormal morphology of colonic ICCs may contribute to the pathogenesis of refractory constipation. Children with refractory constipation exhibited significant variations in microbiota composition across various taxonomic levels compared to the healthy control group. Our findings contribute valuable insights into pathophysiological mechanism underlying refractory constipation and provide evidence to support the exploration of novel therapeutic strategies for affected children.
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Affiliation(s)
- Yi Yuan
- Department of Pediatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
| | - Yan Lu
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
| | - Zhihua Zhang
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
| | - Weixia Cheng
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
| | - Kunlong Yan
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
| | - Yucan Zheng
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
| | - Yu Jin
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
| | - Zhifeng Liu
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.
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Hussain A, Zhang Z, Yu J, Wei R, Arshad H, Lew J, Jagan C, Wang Y, Chen JH, Huizinga JD. Haustral rhythmic motor patterns of the human large bowel revealed by ultrasound. Am J Physiol Gastrointest Liver Physiol 2023; 325:G295-G305. [PMID: 37461842 DOI: 10.1152/ajpgi.00068.2023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 06/16/2023] [Accepted: 06/22/2023] [Indexed: 08/31/2023]
Abstract
Effective and widely available strategies are needed to diagnose colonic motility dysfunction. We investigated whether ultrasonography could generate spatiotemporal maps combined with motor pattern frequency analysis, to become a noninvasive method to characterize human colon motor patterns. Abdominal colonic ultrasonography was performed on healthy subjects (N = 7), focusing on the detailed recording of spontaneous haustral activities. We developed image segmentation and frequency analysis software to analyze the motor patterns captured. Ultrasonography recordings of the ascending, transverse, and descending colon identified three distinct rhythmic motor patterns: the 1 cycle/min and the 3 cycles/min cyclic motor pattern were seen throughout the whole colon, whereas the 12 cycles/min cyclic motor pattern was identified in the ascending colon. The rhythmic motor patterns of the human colon that are associated with interstitial cells of Cajal-associated pacemaking activity can be accurately identified and quantified using ultrasound.NEW & NOTEWORTHY Ultrasonography in the clinical field is an underutilized tool for assessing colonic motility; however, with the addition of frequency analysis techniques, it provides a method to identify human colonic motor patterns. Here we report on the 1, 3, and 12 cpm rhythmic motor patterns. Ultrasound has the potential to become a bedside assessment for colonic dysmotility and may reveal the health of interstitial cells of Cajal (ICC) pacemaker activities.
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Affiliation(s)
- Amer Hussain
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Zhenyu Zhang
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
- Department of Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada
| | - Jennifer Yu
- Biomedical Engineering, University of Waterloo, Waterloo, Ontario, Canada
| | - Ruihan Wei
- Biomedical Engineering, University of Waterloo, Waterloo, Ontario, Canada
| | - Hamza Arshad
- Biomedical Engineering, University of Waterloo, Waterloo, Ontario, Canada
| | - Jinhwan Lew
- Biomedical Engineering, University of Waterloo, Waterloo, Ontario, Canada
| | - Cierra Jagan
- Biomedical Engineering, University of Waterloo, Waterloo, Ontario, Canada
| | - Yongdong Wang
- Department of Radiology, McMaster University, Hamilton, Ontario, Canada
| | - Ji-Hong Chen
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Jan D Huizinga
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
- Department of Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada
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10
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Hibberd TJ, Ramsay S, Spencer-Merris P, Dinning PG, Zagorodnyuk VP, Spencer NJ. Circadian rhythms in colonic function. Front Physiol 2023; 14:1239278. [PMID: 37711458 PMCID: PMC10498548 DOI: 10.3389/fphys.2023.1239278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 08/17/2023] [Indexed: 09/16/2023] Open
Abstract
A rhythmic expression of clock genes occurs within the cells of multiple organs and tissues throughout the body, termed "peripheral clocks." Peripheral clocks are subject to entrainment by a multitude of factors, many of which are directly or indirectly controlled by the light-entrainable clock located in the suprachiasmatic nucleus of the hypothalamus. Peripheral clocks occur in the gastrointestinal tract, notably the epithelia whose functions include regulation of absorption, permeability, and secretion of hormones; and in the myenteric plexus, which is the intrinsic neural network principally responsible for the coordination of muscular activity in the gut. This review focuses on the physiological circadian variation of major colonic functions and their entraining mechanisms, including colonic motility, absorption, hormone secretion, permeability, and pain signalling. Pathophysiological states such as irritable bowel syndrome and ulcerative colitis and their interactions with circadian rhythmicity are also described. Finally, the classic circadian hormone melatonin is discussed, which is expressed in the gut in greater quantities than the pineal gland, and whose exogenous use has been of therapeutic interest in treating colonic pathophysiological states, including those exacerbated by chronic circadian disruption.
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Affiliation(s)
- Timothy J. Hibberd
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Stewart Ramsay
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | | | - Phil G. Dinning
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
- Colorectal Surgical Unit, Division of Surgery, Flinders Medical Centre, Adelaide, SA, Australia
| | | | - Nick J. Spencer
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
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Abstract
Propulsion of contents in the gastrointestinal tract requires coordinated functions of the extrinsic nerves to the gut from the brain and spinal cord, as well as the neuromuscular apparatus within the gut. The latter includes excitatory and inhibitory neurons, pacemaker cells such as the interstitial cells of Cajal and fibroblast-like cells, and smooth muscle cells. Coordination between these extrinsic and enteric neurons results in propulsive functions which include peristaltic reflexes, migrating motor complexes in the small intestine which serve as the housekeeper propelling to the colon the residual content after digestion, and mass movements in the colon which lead to defecation.
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Affiliation(s)
- Gary M Mawe
- Department of Neurological Sciences, The University of Vermont, Burlington, Vermont
| | - Kenton M Sanders
- Department of Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, Reno, Nevada
| | - Michael Camilleri
- Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota
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12
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Wiklendt L, Mohd Rosli R, Kumar R, Paskaranandavadivel N, Bampton PA, Maslen L, Costa M, Brookes SJ, O'Grady G, Dinning PG. Inhibited postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 2023; 325:G62-G79. [PMID: 37162180 DOI: 10.1152/ajpgi.00114.2022] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 05/08/2023] [Accepted: 05/08/2023] [Indexed: 05/11/2023]
Abstract
Patients with irritable bowel syndrome (IBS) have recurrent lower abdominal pain, associated with altered bowel habit (diarrhea and/or constipation). As bowel habit is altered, abnormalities in colonic motility are likely to contribute; however, characterization of colonic motor patterns in patients with IBS remains poor. Utilizing fiber-optic manometry, we aimed to characterize distal colonic postprandial colon motility in diarrhea-predominant IBS. After an overnight fast, a 72-sensor (spaced at 1-cm intervals) manometry catheter was colonoscopically placed to the proximal colon, in 13 patients with IBS-D and 12 healthy adults. Recordings were taken for 2 h pre and post a 700 kcal meal. Data were analyzed with our two developed automated techniques. In both healthy adults and patients with IBS-D, the dominant frequencies of pressure waves throughout the colon are between 2 and 4 cycles per minute (cpm) and the power of these frequencies increased significantly after a meal. Although these pressure waves formed propagating contractions in both groups, the postprandial propagating contraction increase was significantly smaller in patients compared with healthy adults. In healthy adults during the meal period, retrograde propagation between 2 and 8 cpm was significantly greater than antegrade propagation at the same frequencies. This difference was not observed in IBS-D. Patients with IBS-D show reduced prevalence of the retrograde cyclic motor pattern postprandially compared with the marked prevalence in healthy adults. We hypothesize that this reduction may allow premature rectal filling, leading to postprandial urgency and diarrhea.NEW & NOTEWORTHY Compared with healthy adults this study has shown a significant reduction in the prevalence of the postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome. We hypothesize that this altered motility may allow for premature rectal filling which contributes to the postprandial urgency and diarrhea experienced by these patients.
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Affiliation(s)
- Lukasz Wiklendt
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Reizal Mohd Rosli
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Raghu Kumar
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
| | | | - Peter A Bampton
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Lyn Maslen
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Marcello Costa
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Simon J Brookes
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Greg O'Grady
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Phil G Dinning
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
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13
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Wang THH, Tokhi A, Gharibans A, Evennett N, Beban G, Schamberg G, Varghese C, Calder S, Duong C, O'Grady G. Non-invasive thoracoabdominal mapping of postoesophagectomy conduit function. BJS Open 2023; 7:7153161. [PMID: 37146206 PMCID: PMC10162678 DOI: 10.1093/bjsopen/zrad036] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 02/26/2023] [Indexed: 05/07/2023] Open
Affiliation(s)
- Tim Hsu-Han Wang
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Ashraf Tokhi
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Armen Gharibans
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - Nicholas Evennett
- Department of Surgery, Auckland City Hospital, Auckland, New Zealand
| | - Grant Beban
- Department of Surgery, Auckland City Hospital, Auckland, New Zealand
| | - Gabriel Schamberg
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Chris Varghese
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Stefan Calder
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Cuong Duong
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Greg O'Grady
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
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14
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Hyperactive Distal Colonic Motility and Recovery Patterns Following Right Colectomy: A High-Resolution Manometry Study. Dis Colon Rectum 2023; 66:579-590. [PMID: 35499821 DOI: 10.1097/dcr.0000000000002356] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Postoperative ileus results in morbidity, prolonged hospitalization, and increased health care expenditure. However, the underlying abnormalities in motility remain poorly understood. Recent high-resolution manometry studies demonstrated that the distal colon becomes hyperactive with a cyclic motor pattern postoperatively, but they did not track this activity beyond 16 hours after surgery. OBJECTIVE This study used high-resolution manometry to evaluate distal colonic motility during the first 4 days after right-sided colectomy. DESIGN An observational study of perioperative high-resolution colonic manometry using a 36-sensor catheter with 1-cm resolution. SETTING A single tertiary hospital. PATIENTS Adult patients undergoing elective laparoscopic or open right-sided colonic resection. MAIN OUTCOME MEASURES Occurrence of distal colonic motor patterns during the perioperative period, defined according to a published classification system. Clinical markers of gut recovery included time to first stool, oral diet, and prolonged postoperative ileus. RESULTS Seven patients underwent perioperative manometry recordings. Hyperactive cyclic motor patterns emerged intraoperatively and peaked in the first 12 hours postoperatively, occupying 81.8% ± 3.9% of the recording. This gradually returned to normal during the first 4 days, reaching 19.0% ± 4.4% ( p = 0.002). No patient had a bowel movement before this hyperactivity resolved. High-amplitude propagating sequences were absent in early postoperative recordings, and their return temporally correlated with the passage of stool. Abnormal high-amplitude repetitive 0.5 to 1 cycle per minute activity was observed in the left colon of 1 patient with prolonged ileus. LIMITATIONS The invasive nature of recordings limited this study to a small sample size. CONCLUSIONS Cyclic motor patterns are markedly hyperactive in the distal colon after right-sided colectomy and resolve during the first 4 postoperative days. High-amplitude propagating sequences are inhibited by surgery and gradually recover. Bowel function may not return until these changes resolve. Other abnormal repetitive hyperactive patterns could contribute to the development of prolonged ileus. See Video Abstract at http://links.lww.com/DCR/B967 . MOTILIDAD HIPERACTIVA DEL COLON DISTAL Y PATRONES DE RECUPERACIN DESPUS DE COLECTOMA DERECHA UN ESTUDIO DE MANOMETRA DE ALTA RESOLUCIN ANTECEDENTES:El íleo post-operatorio produce una morbilidad significativa, una hospitalización prolongada y un aumento del gasto sanitario. Sin embargo, las anomalías subyacentes en la motilidad siguen siendo poco conocidas. Estudios recientes de manometría de alta resolución demostraron que el colon distal se vuelve hiperactivo con un patrón motor cíclico en el post-operatorio, pero no registraron esta actividad más allá de las 16 horas posteriores a la cirugía.OBJETIVO:Utilizar la manometría de alta resolución para evaluar la motilidad del colon distal durante los primeros cuatro días después de la colectomía del lado derecho.DISEÑO:Estudio observacional de pacientes sometidos a manometría colónica perioperatoria de alta resolución mediante catéter de 36 sensores con 1 cm de resolución.AJUSTE:Un solo hospital terciario.PACIENTES:Pacientes adultos sometidos a resección laparoscópica o abierta de colon del lado derecho de forma electiva.PRINCIPALES MEDIDAS DE RESULTADO:AAparición de patrones motores del colon distal durante el período perioperatorio, definidos según un sistema de clasificación publicado. Los marcadores clínicos de recuperación intestinal incluyeron, tiempo hasta la primera evacuación, dieta oral e íleo posoperatorio prolongado.RESULTADOS:Siete pacientes fueron sometidos a registros de manometría perioperatoria. Los patrones motores cíclicos hiperactivos emergieron intraoperatoriamente y alcanzaron su punto máximo en las primeras 12 horas post-operatorias, ocupando 81,8 ± 3,9% del registro. Esto volvió gradualmente a la normalidad durante los primeros cuatro días, alcanzando el 19,0 ± 4,4% (p = 0,002). Ningún paciente tuvo una evacuación intestinal antes de que se resolviera esta hiperactividad. Las secuencias de propagación de alta amplitud estaban ausentes en las grabaciones post-operatorias tempranas y su retorno se correlacionó temporalmente con el paso de las heces. Se observó actividad anormal de alta amplitud repetitiva de 0,5-1 ciclo / minuto en el colon izquierdo de un paciente con íleo prolongado.LIMITACIONES:La naturaleza invasiva de las grabaciones limitó este estudio a un tamaño de muestra pequeño.CONCLUSIONES:Los patrones motores cíclicos son marcadamente hiperactivos en el colon distal después de la colectomía del lado derecho y se resuelven gradualmente durante los primeros cuatro días posoperatorios. Las secuencias de propagación de gran amplitud se inhiben mediante cirugía y se recuperan gradualmente. Es posible que la función intestinal no regrese hasta que estos cambios se resuelvan. Otros patrones hiperactivos repetitivos anormales podrían contribuir al desarrollo de íleo prolongado. Consulte Video Resumen en http://links.lww.com/DCR/B967 . (Traducción-Dr. Mauricio Santamaria ).
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15
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Evans-Barns HME, Tien MY, Trajanovska M, Safe M, Hutson JM, Dinning PG, King SK. Post-Operative Anorectal Manometry in Children following Anorectal Malformation Repair: A Systematic Review. J Clin Med 2023; 12:jcm12072543. [PMID: 37048627 PMCID: PMC10094903 DOI: 10.3390/jcm12072543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 03/02/2023] [Accepted: 03/16/2023] [Indexed: 03/30/2023] Open
Abstract
Despite surgical correction, children with anorectal malformations may experience long-term bowel dysfunction, including fecal incontinence and/or disorders of evacuation. Anorectal manometry is the most widely used test of anorectal function. Although considerable attention has been devoted to its application in the anorectal malformation cohort, there have been few attempts to consolidate the findings obtained. This systematic review aimed to (1) synthesize and evaluate the existing data regarding anorectal manometry results in children following anorectal malformation repair, and (2) evaluate the manometry protocols utilized, including equipment, assessment approach, and interpretation. We reviewed four databases (Embase, MEDLINE, the Cochrane Library, and PubMed) for relevant articles published between 1 January 1985 and 10 March 2022. Studies reporting post-operative anorectal manometry in children (<18 years) following anorectal malformation repair were evaluated for eligibility. Sixty-three studies were eligible for inclusion. Of the combined total cohort of 2155 patients, anorectal manometry results were reported for 1755 children following repair of anorectal malformations. Reduced resting pressure was consistently identified in children with anorectal malformations, particularly in those with more complex malformation types and/or fecal incontinence. Significant variability was identified in relation to manometry equipment, protocols, and interpretation. Few studies provided adequate cohort medical characteristics to facilitate interpretation of anorectal manometry findings within the context of the broader continence mechanism. This review highlights a widespread lack of standardization in the anorectal manometry procedure used to assess anorectal function in children following anorectal malformation repair. Consequently, interpretation and comparison of findings, both within and between institutions, is exceedingly challenging, if not impossible. Standardized manometry protocols, accompanied by a consistent approach to analysis, including definitions of normality and abnormality, are essential to enhance the comparability and clinical relevance of results.
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16
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Oh HK, Sung TS, Ryoo SB, Park KJ. Regional Differences in Intestinal Contractile Responses to Radial Stretch in the Human Lower Gastrointestinal Tract. J Neurogastroenterol Motil 2023; 29:113-121. [PMID: 36437512 PMCID: PMC9837542 DOI: 10.5056/jnm21236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 07/01/2022] [Accepted: 08/06/2022] [Indexed: 12/03/2022] Open
Abstract
Background/Aims Radial stretch evokes an increase or decrease in contractions in the lower gastrointestinal tract via mechanosensory enteric neurons that project into the muscle layers. We aim to elucidate the differences in stretch reflexes according to their location in the human colon. Methods We used healthy intestinal smooth muscle tissue excised during elective colon cancer surgery. Conventional intracellular recordings from colonic muscle cells and tension recordings of colonic segments were performed. Radial stretch was evoked through balloon catheter inflation. Changes in the membrane potential and frequency, amplitude, and area under the curve of muscle contractions were recorded before and after the radial stretch at proximal and distal segment sites. Results In intracellular circular muscle recordings, hyperpolarization was noted at the distal site of sigmoid colonic segments after radial stretch, in contrast to depolarization at all other sites. In tension recordings at proximal ascending or sigmoid colonic segment sites, contractile activation was observed with statistically significant increases in the frequency, amplitude, and area under the curve after radial stretch. Distal sites of ascending and sigmoid colonic segments showed increase and decrease in contraction, respectively. Conclusion Radial stretch in the human colon (in vitro) evokes excitatory activity at both proximal and distal sites of the ascending colon and at the proximal site of the sigmoid colon, whereas it elicits inhibitory activity at the distal site of the sigmoid colon.
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Affiliation(s)
- Heung-Kwon Oh
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
| | - Tae Sik Sung
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea,Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea
| | - Seung-Bum Ryoo
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Kyu Joo Park
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea,Correspondence: Kyu Joo Park, MD, PhD, Department of Surgery, Seoul National University College of Medicine, 101 Daehangno, Jongno-gu, Seoul 03080, Korea, Tel: +82-2-2072-2901, Fax: +82-2-766-3975, E-mail:
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17
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Management of Low Anterior Resection Syndrome (LARS) Following Resection for Rectal Cancer. Cancers (Basel) 2023; 15:cancers15030778. [PMID: 36765736 PMCID: PMC9913853 DOI: 10.3390/cancers15030778] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 01/21/2023] [Accepted: 01/22/2023] [Indexed: 02/03/2023] Open
Abstract
INTRODUCTION A total of 60-80% of patients undergoing rectal resection (mostly as a treatment for rectal cancer) suffer from a variety of partly severe functional problems despite preservation of the anal sphincter. These patients are summarized under the term low anterior resection syndrome (LARS). Preoperative radiotherapy, vascular dissection and surgical excision of the low rectum and mesorectum lead, alone or all together, to a significant impairment of colonic and (neo-) rectal motility. This results in a variety of symptoms (multiple defecation episodes, recurrent episodes of urge, clustering, incontinence, etc.) which are associated with severe impairment of quality of life (QOL). METHODS This narrative review summarizes the present state of knowledge regarding the pathophysiology of LARS as well as the evidence for the available treatment options to control the symptoms resulting from this condition. RESULTS A review of the literature (Medline, Pubmed) reveals a variety of treatment options available to control symptoms of LARS. Medical therapy, with or without dietary modification, shows only a modest effect. Pelvic floor rehabilitation consisting of muscle exercise techniques as well as biofeedback training has been associated with improvement in LARS scores and incontinence, albeit with limited scientific evidence. Transanal irrigation (TAI) has gained interest as a treatment modality for patients with LARS due to an increasing number of promising data from recently published studies. Despite this promising observation, open questions about still-unclear issues of TAI remain under debate. Neuromodulation has been applied in LARS only in a few studies with small numbers of patients and partly conflicting results. CONCLUSION LARS is a frequent problem after sphincter-preserving rectal surgery and leads to a marked impairment of QOL. Due to the large number of patients suffering from this condition, mandatory identification, as well as treatment of affected patients, must be considered during surgical as well as oncological follow-up. The use of a standardized treatment algorithm will lead to sufficient control of symptoms and a high probability of a marked improvement in QOL.
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18
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Abdalla TSA, Zimmermann M, Weisheit L, Thomaschewski M, Deichmann S, Nolde J, Keck T, Benecke C. Long-term functional outcome after tubular laparoscopic sigmoid resection for diverticular disease. Int J Colorectal Dis 2023; 38:14. [PMID: 36645511 PMCID: PMC9842559 DOI: 10.1007/s00384-023-04311-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/08/2023] [Indexed: 01/17/2023]
Abstract
PURPOSE Sigmoid resection for diverticular disease is a frequent surgical procedure in the Western world. However, long-term bowel function after sigmoid resection has been poorly described in the literature. This study aims to assess the long-term bowel function after tubular sigmoid resection with preservation of inferior mesenteric artery (IMA) for diverticular disease. METHODS We retrospectively identified patients who underwent sigmoid resection for diverticular disease between 2002 and 2012 at a tertiary referral center in northern Germany. Using well-validated questionnaires, bowel function was assessed for fecal urgency, incontinence, and obstructed defecation. The presence of bowel dysfunction was compared to baseline characteristics and perioperative outcome. RESULTS Two hundred and thirty-eight patients with a mean age of 59.2 ± 10 years responded to our survey. The follow-up was conducted 117 ± 32 months after surgery. At follow-up, 44 patients (18.5%) had minor LARS (LARS 21-29) and 35 (15.1%) major LARS (LARS ≥ 30-42), 35 patients had moderate-severe incontinence (CCIS ≥ 7), and 2 patients (1%) had overt obstipation (CCOS ≥ 15). The multivariate analysis showed that female gender was the only prognostic factor for long-term incontinence (CCIS ≥ 7), and ASA score was the only preoperative prognostic factor for the presence of major LARS at follow-up. CONCLUSION Sigmoid resection for diverticular disease can be associated with long-term bowel dysfunction, even with tubular dissection and preservation of IMA. These findings suggest intercolonic mechanisms of developing symptoms of bowel dysfunction after disruption of the colorectal continuity that are so far summarized as "sigmoidectomy syndrome."
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Affiliation(s)
- Thaer S A Abdalla
- Department of General Surgery, at the University Medical Center Schleswig Holstein, 23562, Lübeck, Germany.
- Department of General Surgery, University Medical Center Schleswig Holstein, Campus Lübeck, Ratzeburger Alle 160, 23564, Lübeck, Germany.
| | - Markus Zimmermann
- Department of General Surgery, at the University Medical Center Schleswig Holstein, 23562, Lübeck, Germany
- Department of General Surgery, University Medical Center Schleswig Holstein, Campus Lübeck, Ratzeburger Alle 160, 23564, Lübeck, Germany
| | - Lena Weisheit
- Department of General Surgery, at the University Medical Center Schleswig Holstein, 23562, Lübeck, Germany
| | - Michael Thomaschewski
- Department of General Surgery, at the University Medical Center Schleswig Holstein, 23562, Lübeck, Germany
| | - Steffen Deichmann
- Department of General Surgery, at the University Medical Center Schleswig Holstein, 23562, Lübeck, Germany
| | - Jan Nolde
- Department of General Surgery, at the University Medical Center Schleswig Holstein, 23562, Lübeck, Germany
| | - Tobias Keck
- Department of General Surgery, at the University Medical Center Schleswig Holstein, 23562, Lübeck, Germany
| | - Claudia Benecke
- Department of General Surgery, at the University Medical Center Schleswig Holstein, 23562, Lübeck, Germany.
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19
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Trzpis M, Sun G, Chen JH, Huizinga JD, Broens P. Novel insights into physiological mechanisms underlying fecal continence. Am J Physiol Gastrointest Liver Physiol 2023; 324:G1-G9. [PMID: 36283962 DOI: 10.1152/ajpgi.00313.2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The machinery maintaining fecal continence prevents involuntary loss of stool and is based on the synchronized interplay of multiple voluntary and involuntary mechanisms, dependent on cooperation between motor responses of the musculature of the colon, pelvic floor, and anorectum, and sensory and motor neural pathways. Knowledge of the physiology of fecal continence is key toward understanding the pathophysiology of fecal incontinence. The idea that involuntary contraction of the internal anal sphincter is the primary mechanism of continence and that the external anal sphincter supports continence only by voluntary contraction is outdated. Other mechanisms have come to the forefront, and they have significantly changed viewpoints on the mechanisms of continence and incontinence. For instance, involuntary contractions of the external anal sphincter, the puborectal muscle, and the sphincter of O'Beirne have been proven to play a role in fecal continence. Also, retrograde propagating cyclic motor patterns in the sigmoid and rectum promote retrograde transit to prevent the continuous flow of content into the anal canal. With this review, we aim to give an overview of primary and secondary mechanisms controlling fecal continence and evaluate the strength of evidence.
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Affiliation(s)
- Monika Trzpis
- Department of Surgery, Anorectal Physiology Laboratory, University of Groningen, University Medical Center, Groningen, The Netherlands
| | - Ge Sun
- Department of Surgery, Anorectal Physiology Laboratory, University of Groningen, University Medical Center, Groningen, The Netherlands
| | - Ji-Hong Chen
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Canada
| | - Jan D Huizinga
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Canada
| | - Paul Broens
- Department of Surgery, Anorectal Physiology Laboratory, University of Groningen, University Medical Center, Groningen, The Netherlands.,Division of Pediatric Surgery, Department of Surgery, University of Groningen, University Medical Center, Groningen, The Netherlands
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20
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Evans-Barns HME, Tien MY, Trajanovska M, Safe M, Hutson JM, Dinning PG, King SK. Post-operative colonic manometry in children with anorectal malformations: A systematic review. Neurogastroenterol Motil 2022; 34:e14415. [PMID: 35699343 PMCID: PMC10078517 DOI: 10.1111/nmo.14415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 03/07/2022] [Accepted: 04/20/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND Children with anorectal malformations may experience constipation and fecal incontinence following repair. The contribution of altered anorectal function to these persistent symptoms is relatively intuitive; however, colonic motility in this cohort is less well understood. Manometry may be used to directly assess colonic motility. PURPOSE The purpose of this systematic review was to synthesize the available evidence regarding post-operative colonic motility in children with anorectal malformations and evaluate the reported equipment and protocols used to perform colonic manometry in this cohort. This systematic review was conducted in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We conducted a systematic review of four databases: Embase, MEDLINE, PubMed, and the Cochrane Library (1st January 1985-22nd July 2021). Studies reporting colonic manometry performed in children following anorectal malformation repair were assessed for eligibility. Data were extracted independently by two authors. Four studies were eligible for inclusion. Of the combined total cohort of 151 children, post-operative colonic manometry was conducted in 35. Insufficient reporting of medical characteristics, bowel function, and manometric outcomes restricted comparison between studies, and limited clinical applicability. No results from high-resolution colonic manometry were identified. Despite the prevalence of post-operative bowel dysfunction in children with repaired anorectal malformations, this systematic review highlighted the markedly limited evidence regarding post-operative colonic motility. This cohort may benefit from assessment with high-resolution techniques; however, future work must emphasize adherence to standardized manometry protocols, and include robust reporting of surgical characteristics, bowel function, and manometric outcomes.
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Affiliation(s)
- Hannah M E Evans-Barns
- Department of Paediatric Surgery, The Royal Children's Hospital, Melbourne, Victoria, Australia.,Surgical Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
| | - Melissa Y Tien
- Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
| | - Misel Trajanovska
- Department of Paediatric Surgery, The Royal Children's Hospital, Melbourne, Victoria, Australia.,Surgical Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
| | - Mark Safe
- Department of Gastroenterology and Clinical Nutrition, The Royal Children's Hospital, Melbourne, Victoria, Australia
| | - John M Hutson
- Surgical Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.,Department of Urology, The Royal Children's Hospital, Melbourne, Victoria, Australia
| | - Phil G Dinning
- Department of Surgery, College of Medicine and Public Health, The Flinders University and Flinders Medical Centre, Bedford Park, South Australia, Australia
| | - Sebastian K King
- Department of Paediatric Surgery, The Royal Children's Hospital, Melbourne, Victoria, Australia.,Surgical Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
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21
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Lin AY, Varghese C, Paskaranandavadivel N, Seo S, Du P, Dinning P, Bissett IP, O'Grady G. Faecal incontinence is associated with an impaired rectosigmoid brake and improved by sacral neuromodulation. Colorectal Dis 2022; 24:1556-1566. [PMID: 35793162 PMCID: PMC10084032 DOI: 10.1111/codi.16249] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/04/2022] [Accepted: 05/20/2022] [Indexed: 01/07/2023]
Abstract
BACKGROUND The rectosigmoid brake, characterised by retrograde cyclic motor patterns on high-resolution colonic manometry, has been postulated as a contributor to the maintenance of bowel continence. Sacral neuromodulation (SNM) is an effective therapy for faecal incontinence, but its mechanism of action is unclear. This study aims to investigate the colonic motility patterns in the distal colon of patients with faecal incontinence, and how these are modulated by SNM. METHODS A high-resolution fibreoptic colonic manometry catheter, containing 36 sensors spaced at 1-cm intervals, was positioned in patients with faecal incontinence undergoing stage 1 SNM. One hour of pre- and post meal recordings were obtained followed by pre- and post meal recordings with suprasensory SNM. A 700-kcal meal was given. Data were analysed to identify propagating contractions. RESULTS Fifteen patients with faecal incontinence were analysed. Patients had an abnormal meal response (fewer retrograde propagating contractions compared to controls; p = 0.027) and failed to show a post meal increase in propagating contractions (mean 17 ± 6/h premeal vs. 22 ± 9/h post meal, p = 0.438). Compared to baseline, SNM significantly increased the number of retrograde propagating contractions in the distal colon (8 ± 3/h premeal vs. 14 ± 3/h premeal with SNM, p = 0.028). Consuming a meal did not further increase the number of propagating contractions beyond the baseline upregulating effect of SNM. CONCLUSION The rectosigmoid brake was suppressed in this cohort of patients with faecal incontinence. SNM may exert a therapeutic effect by modulating this rectosigmoid brake.
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Affiliation(s)
- Anthony Y Lin
- Department of Surgery, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Chris Varghese
- Department of Surgery, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | | | - Sean Seo
- Department of Surgery, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Peng Du
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - Phil Dinning
- Department of Gastroenterology, Flinders Medical Centre, Bedford Park, South Australia, Australia.,Discipline of Human Physiology, Flinders University, Adelaide, South Australia, Australia
| | - Ian P Bissett
- Department of Surgery, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Greg O'Grady
- Department of Surgery, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.,Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
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22
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Johnson ME, Humenick A, Peterson RA, Costa M, Wattchow DA, Sia TC, Dinning PG, Brookes SJH. Characterisation of parasympathetic ascending nerves in human colon. Front Neurosci 2022; 16:1072002. [PMID: 36532291 PMCID: PMC9752816 DOI: 10.3389/fnins.2022.1072002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 11/11/2022] [Indexed: 11/19/2023] Open
Abstract
Background In the human large bowel, sacral parasympathetic nerves arise from S2 to S4, project to the pelvic plexus ("hypogastric plexus") and have post-ganglionic axons entering the large bowel near the rectosigmoid junction. They then run long distances orally or aborally within the bowel wall forming "ascending nerves" or "shunt fascicles" running in the plane of the myenteric plexus. They form bundles of nerve fibres that can be distinguished from the myenteric plexus by their straight orientation, tendency not to merge with myenteric ganglia and greater width. Aim To identify reliable marker(s) to distinguish these bundles of ascending nerves from other extrinsic and intrinsic nerves in human colon. Methods Human colonic segments were obtained with informed consent, from adult patients undergoing elective surgery (n = 21). Multi-layer immunohistochemical labelling with neurofilament-H (NF200), myelin basic protein (MBP), von Willebrand factor (vWF), and glucose transporter 1 (GLUT1), and rapid anterograde tracing with biotinamide, were used to compare ascending nerves and lumbar colonic nerves. Results The rectosigmoid and rectal specimens had 6-11 ascending nerves spaced around their circumference. Distal colon specimens typically had 1-3 ascending nerves, with one located near the mesenteric taenia coli. No ascending nerves were observed in ascending colon specimens. GLUT1 antisera labelled both sympathetic lumbar colonic nerves and ascending nerves in the gut wall. Lumbar colonic nerves joined the myenteric plexus and quickly lost GLUT1 labelling, whereas GLUT1 staining labelled parasympathetic ascending nerves over many centimetres. Conclusion Ascending nerves can be distinguished in the colorectum of humans using GLUT1 labelling combined with NF200.
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Affiliation(s)
- Michaela E. Johnson
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Adam Humenick
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Rochelle A. Peterson
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Marcello Costa
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - David A. Wattchow
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Tiong Cheng Sia
- Colorectal Surgical Unit, Division of Surgery, Flinders Medical Centre, Bedford Park, SA, Australia
| | - Phil G. Dinning
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Bedford Park, SA, Australia
| | - Simon J. H. Brookes
- College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
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23
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Asnong A, Tack J, Devoogdt N, De Groef A, Geraerts I, D'Hoore A. Exploring the pathophysiology of LARS after low anterior resection for rectal cancer with high-resolution colon manometry. Neurogastroenterol Motil 2022; 34:e14432. [PMID: 35866548 DOI: 10.1111/nmo.14432] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 05/16/2022] [Accepted: 06/10/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND A total mesorectal excision for rectal cancer-although nerve- and sphincter-sparing-can give rise to significant bowel symptoms, commonly referred to as low anterior resection syndrome (LARS). The exact pathophysiology of this syndrome still remains largely unknown, and the impact of radical surgery on colonic motility has only been scarcely investigated. METHODS High-resolution colon manometry was performed in patients, 12-24 months after restoration of transit. Patients were divided into two groups: patients with major LARS and no/minor LARS, according to the LARS-score. Colonic motor patterns were compared, and the relationship of these patterns with the LARS-scores was investigated. KEY RESULTS Data were analyzed in 18 patients (9 no/minor LARS, 9 major LARS). Cyclic short antegrade motor patterns did occur more in patients with major LARS (total: p = 0.022; post-bisacodyl: p = 0.004) and were strongly correlated to LARS-scores after administering bisacodyl (p < 0.001). High amplitude propagating contractions (HAPC's) that started in the proximal colon and ended in the mid-section of the colon occurred significantly less in patients with major LARS compared with patients with no/minor LARS (p = 0.015). CONCLUSIONS AND INFERENCES The occurrence of more cyclic short antegrade motor patterns and less HAPC's (from the proximal to the mid-colon) is more prevalent in patients with major LARS. These findings help to understand the differences in pathophysiology in patients developing major versus no/minor bowel complaints after TME for rectal cancer.
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Affiliation(s)
- Anne Asnong
- Department of Rehabilitation Sciences, Faculty of Movement and Rehabilitation Sciences, Leuven, Belgium
| | - Jan Tack
- Department of Chronic Diseases, Metabolism and Ageing, Faculty of Medicine, Leuven, Belgium.,Department of Translational Research in Gastrointestinal Disorders, University Hospitals Leuven, Leuven, Belgium
| | - Nele Devoogdt
- Center for lymphedema, University Hospitals Leuven, Leuven, Belgium.,Department of Rehabilitation Sciences, KU Leuven - University of Leuven, Leuven, Belgium
| | - An De Groef
- Department of Rehabilitation Sciences, KU Leuven - University of Leuven, Leuven, Belgium.,Department of Rehabilitation Sciences, University of Antwerp, Antwerp, Belgium.,International Research Group Pain in Motion, Leuven, Belgium
| | - Inge Geraerts
- Department of Rehabilitation Sciences, Faculty of Movement and Rehabilitation Sciences, Leuven, Belgium.,Department of Physical Medicine and Rehabilitation, University Hospitals Leuven
| | - André D'Hoore
- Department of Oncology, Faculty of Medicine, Leuven, Belgium.,Department of Abdominal Surgery, University Hospitals Leuven, Leuven, Belgium
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24
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Varghese C, Wells CI, Bissett IP, O'Grady G, Keane C. The role of colonic motility in low anterior resection syndrome. Front Oncol 2022; 12:975386. [PMID: 36185226 PMCID: PMC9523793 DOI: 10.3389/fonc.2022.975386] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 08/29/2022] [Indexed: 11/13/2022] Open
Abstract
Low anterior resection syndrome (LARS) describes the symptoms and experiences of bowel dysfunction experienced by patients after rectal cancer surgery. LARS is a complex and multifactorial syndrome exacerbated by factors such as low anastomotic height, defunctioning of the colon and neorectum, and radiotherapy. There has recently been growing awareness and understanding regarding the role of colonic motility as a contributing mechanism for LARS. It is well established that rectosigmoid motility serves an important role in coordinating rectal filling and maintaining continence. Resection of the rectosigmoid may therefore contribute to LARS through altered distal colonic and neorectal motility. This review evaluates the role of colonic motility within the broader pathophysiology of LARS and outlines future directions of research needed to enable targeted therapy for specific LARS phenotypes.
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Affiliation(s)
- Chris Varghese
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Cameron I Wells
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
- Department of General Surgery, Counties Manukau District Health Board, Auckland, New Zealand
| | - Ian P Bissett
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
- Department of Surgery, Auckland City Hospital, Auckland, New Zealand
| | - Gregory O'Grady
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Celia Keane
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
- Department of Surgery, Whangārei Hospital, Whangarei, New Zealand
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25
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Bharucha AE, Knowles CH, Mack I, Malcolm A, Oblizajek N, Rao S, Scott SM, Shin A, Enck P. Faecal incontinence in adults. Nat Rev Dis Primers 2022; 8:53. [PMID: 35948559 DOI: 10.1038/s41572-022-00381-7] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/29/2022] [Indexed: 11/09/2022]
Abstract
Faecal incontinence, which is defined by the unintentional loss of solid or liquid stool, has a worldwide prevalence of ≤7% in community-dwelling adults and can markedly impair quality of life. Nonetheless, many patients might not volunteer the symptom owing to embarrassment. Bowel disturbances, particularly diarrhoea, anal sphincter trauma (obstetrical injury or previous surgery), rectal urgency and burden of chronic illness are the main risk factors for faecal incontinence; others include neurological disorders, inflammatory bowel disease and pelvic floor anatomical disturbances. Faecal incontinence is classified by its type (urge, passive or combined), aetiology (anorectal disturbance, bowel symptoms or both) and severity, which is derived from the frequency, volume, consistency and nature (urge or passive) of stool leakage. Guided by the clinical features, diagnostic tests and therapies are implemented stepwise. When simple measures (for example, bowel modifiers such as fibre supplements, laxatives and anti-diarrhoeal agents) fail, anorectal manometry and other tests (endoanal imaging, defecography, rectal compliance and sensation, and anal neurophysiological tests) are performed as necessary. Non-surgical options (diet and lifestyle modification, behavioural measures, including biofeedback therapy, pharmacotherapy for constipation or diarrhoea, and anal or vaginal barrier devices) are often effective, especially in patients with mild faecal incontinence. Thereafter, perianal bulking agents, sacral neuromodulation and other surgeries may be considered when necessary.
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Affiliation(s)
- Adil E Bharucha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
| | - Charles H Knowles
- Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Queen Mary University of London, London, UK
| | - Isabelle Mack
- University Hospital, Department of Psychosomatic Medicine, Tübingen, Germany
| | - Allison Malcolm
- Department of Gastroenterology, Royal North Shore Hospital and University of Sydney, Sydney, New South Wales, Australia
| | - Nicholas Oblizajek
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Satish Rao
- Department of Gastroenterology, University of Georgia, Augusta, GA, USA
| | - S Mark Scott
- Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Queen Mary University of London, London, UK
| | - Andrea Shin
- Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, IN, USA
| | - Paul Enck
- University Hospital, Department of Psychosomatic Medicine, Tübingen, Germany.
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26
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Church JM. Re: Four different ileorectal anastomotic configurations following total colectomy. ANZ J Surg 2022; 92:1960. [PMID: 35950663 DOI: 10.1111/ans.17681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 12/06/2020] [Indexed: 11/29/2022]
Affiliation(s)
- James M Church
- Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio, USA
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27
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de Gaay Fortman DPE, Kroon HM, Bedrikovetski S, Fitzsimmons TR, Dudi-Venkata NN, Sammour T. A snapshot of intraoperative conditions to predict prolonged postoperative ileus after colorectal surgery. ANZ J Surg 2022; 92:2199-2206. [PMID: 35579059 DOI: 10.1111/ans.17784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 03/28/2022] [Accepted: 04/15/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND The cause of prolonged postoperative ileus (PPOI) is multifactorial. The influence of preoperative factors on PPOI has been well documented, but little is known about the impact of intraoperative conditions. The aim of this study was to investigate the influence of intraoperative factors on PPOI in patients undergoing colorectal surgery. METHODS The LekCheck study database of the Colorectal Unit at the Royal Adelaide Hospital was analysed. Per patient, over 60 data points were prospectively collected between March 2018 and July 2020. Intraoperative data were collected in theatre during a one-off snapshot measure. Univariate and multivariable logistic regression analyses were performed. RESULTS Data of 336 patients were included. The median age was 66 years and 58.3% were male. Ninety-three patients (27.7%) developed PPOI. Univariate analysis identified the following intraoperative variables as risk-factors of PPOI: greater volumes of intraoperative IV fluid administration (464 versus 415 mL/h for those without PPOI; p = 0.04), side-to-side anastomosis orientation (53.8 versus 41.2%; p = 0.04) and increased perioperative opioid use (6.73 versus 4.11 mg/kg morphine equivalents for patients with and without PPOI, respectively; p = 0.02). Upon multivariable analysis, increased perioperative opioid use remained significant (p = 0.05), as well as the preoperative factors anticoagulation use (p = 0.04) and higher levels of serum total protein (p = 0.02). CONCLUSION This study suggests that intraoperative factors may also contribute to the development of PPOI, but this could not be confirmed in the multivariate analysis. Further studies including larger patient numbers will be required to determine the impact of intraoperative conditions on the development of PPOI.
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Affiliation(s)
- Duveke P E de Gaay Fortman
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia.,Faculty of Medical Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Hidde M Kroon
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia.,Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
| | - Sergei Bedrikovetski
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia.,Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
| | - Tracy R Fitzsimmons
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia.,Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
| | - Nagendra N Dudi-Venkata
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia.,Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
| | - Tarik Sammour
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia.,Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
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28
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Automatic Detection and Segmentation of Colorectal Cancer with Deep Residual Convolutional Neural Network. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:3415603. [PMID: 35341149 PMCID: PMC8947925 DOI: 10.1155/2022/3415603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 02/07/2022] [Indexed: 11/22/2022]
Abstract
Early and automatic detection of colorectal tumors is essential for cancer analysis, and the same is implemented using computer-aided diagnosis (CAD). A computerized tomography (CT) image of the colon is being used to identify colorectal carcinoma. Digital imaging and communication in medicine (DICOM) is a standard medical imaging format to process and analyze images digitally. Accurate detection of tumor cells in the complex digestive tract is necessary for optimal treatment. The proposed work is divided into two phases. The first phase involves the segmentation, and the second phase is the extraction of the colon lesions with the observed segmentation parameters. A deep convolutional neural network (DCNN) based residual network approach for the colon and polyps' segmentation from the CT images is applied over the 2D CT images. The residual stack block is being added to the hidden layers with short skip nuance, which helps to retain spatial information. ResNet-enabled CNN is employed in the current work to achieve complete boundary segmentation of the colon cancer region. The results obtained through segmentation serve as features for further extraction and classification of benign as well as malignant colon cancer. Performance evaluation metrics indicate that the proposed network model has effectively segmented and classified colorectal tumors with dice scores of 91.57% (on average), sensitivity = 98.28, specificity = 98.68, and accuracy = 98.82.
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29
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Lin Z, Yang C, Wang Y, Yan M, Zheng H. Comparison of prolonged postoperative ileus between laparoscopic right and left colectomy under enhanced recovery after surgery: a propensity score matching analysis. World J Surg Oncol 2022; 20:68. [PMID: 35246150 PMCID: PMC8895612 DOI: 10.1186/s12957-022-02504-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 02/03/2022] [Indexed: 11/10/2022] Open
Abstract
Background There were differences in the recovery of bowel function and prolonged postoperative ileus (PPOI) between laparoscopic right colectomy (RC) and left colectomy (LC) under the guidance of enhanced recovery after surgery. Methods We selected 870 patients who underwent elective laparoscopic colectomy from June 2016 to December 2021, including 272 patients who had RC and 598 who had LC. According to 1:1 proportion for propensity score matching and correlation analysis, 247 patients who had RC and 247 who had LC were finally enrolled. Results The incidence of PPOI in all patients was 13.1%. Age, sex, smoking habit, preoperative serum albumin level, operation type, and operation time were the important independent risk factors based on multivariate logistic regression and correlation analysis for PPOI (p<0.05). Age, sex, body mass index, preoperative serum albumin level, operation time, and degree of differentiation between the two groups were significantly different before case matching (p<0.05). There were no statistically significant differences in baseline characteristics and preoperative biochemical parameters between the two groups after case matching (p>0.05). The incidence of PPOI in patients who had RC was 21.9%, while that in patients who had LC was 13.0%. The first flatus, first semi-liquid, and length of stay in LC patients were lower than those in RC patients (p<0.05). Conclusion The return of bowel function in LC was faster than that in RC, and the incidence of PPOI was relatively lower. Therefore, caution should be taken during the early feeding of patients who had laparoscopic RC.
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Affiliation(s)
- Zhenmeng Lin
- Department of Gastrointestinal Surgery, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, No 420 fuma road, Jin' an district, Fuzhou, China
| | - Chunkang Yang
- Department of Gastrointestinal Surgery, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, No 420 fuma road, Jin' an district, Fuzhou, China
| | - Yi Wang
- Department of Gastrointestinal Surgery, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, No 420 fuma road, Jin' an district, Fuzhou, China
| | - Mingfang Yan
- Department of Gastrointestinal Surgery, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, No 420 fuma road, Jin' an district, Fuzhou, China
| | - Huizhe Zheng
- Department of Anesthesiology Surgery, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, No 420 fuma road, Jin' an district, Fuzhou, China.
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30
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Pannemans J, Vanuytsel T, Pauwels A, Rommel N, De Schepper H, Lam TJ, Thys A, Tack J. High-resolution colonic manometry interobserver analysis trial. Neurogastroenterol Motil 2022; 34:e14285. [PMID: 34843634 DOI: 10.1111/nmo.14285] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 03/26/2021] [Accepted: 04/28/2021] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Colonic high-resolution manometry (HRM) is a novel, not widely used diagnostic method used in the final workup of chronic constipation before surgery. Since its introduction, different motor patterns have been defined. However, it remains to be established whether these patterns are easily and reproducibly identified by different investigators. METHODS The primary aim of this study was to determine agreement for motor pattern identification with HRM. To calculate the interobserver agreement (IOA), the Fleiss's kappa statistic for multiple observers was used. Seven participants analyzed 106 one-min time frames, derived from five measurements in healthy volunteers and five in patients with chronic constipation. The time frames were chosen to show a variety and combination of motor patterns consisting of short antegrade, short retrograde, cyclic anterograde, cyclic retrograde, long antegrade, long retrograde, slow retrograde motor pattern, high-amplitude propagating motor patterns, and pancolonic pressurizations. All of the measurements were performed with a solid-state colonic HRM catheter, comprising 40 pressure sensors spaced 2.5 cm apart. RESULTS A median of 10.25 h (range 6-20) were required to analyze all time frames. High-amplitude propagating contractions achieved an almost perfect level of agreement (k = 0.91). Several motor patterns achieved substantial agreement; these included the short antegrade (k = 0.63), long antegrade (k = 0.68), cyclic retrograde (k = 0.70), slow retrograde motor pattern (k = 0.80), and abdominal pressure or movement artifacts (k = 0.67). Moderate agreement was found for short retrograde (k = 0.57), cyclic anterograde (k = 0.59), long retrograde motor patterns (k = 0.59) and simultaneous pressure waves (k = 0.59). CONCLUSION For the majority of motor patterns, the overall IOA for colonic manometry was substantial or high. This high level of agreement supports the use of colonic manometry application in clinical and research settings. Harmonization has the potential to improve agreement for long anterograde motor patterns with high amplitudes and for mixed direction patterns.
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Affiliation(s)
- Jasper Pannemans
- Translational Research Center for Gastrointestinal Disorders (TARGID), KULeuven, Belgium.,Department of Gastroenterology and Hepatology, University Hospital of Leuven, Leuven, Belgium
| | - Tim Vanuytsel
- Translational Research Center for Gastrointestinal Disorders (TARGID), KULeuven, Belgium.,Department of Gastroenterology and Hepatology, University Hospital of Leuven, Leuven, Belgium
| | - Ans Pauwels
- Translational Research Center for Gastrointestinal Disorders (TARGID), KULeuven, Belgium
| | | | - Heiko De Schepper
- Department of Gastroenterology and Hepatology, University Hospital of Antwerp, Edegem, Belgium
| | - Tze J Lam
- Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, The Netherlands
| | - Alexander Thys
- Translational Research Center for Gastrointestinal Disorders (TARGID), KULeuven, Belgium
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders (TARGID), KULeuven, Belgium.,Department of Gastroenterology and Hepatology, University Hospital of Leuven, Leuven, Belgium
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31
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Heitmann PT, Mohd Rosli R, Maslen L, Wiklendt L, Kumar R, Omari TI, Wattchow D, Costa M, Brookes SJ, Dinning PG. High-resolution impedance manometry characterizes the functional role of distal colonic motility in gas transit. Neurogastroenterol Motil 2022; 34:e14178. [PMID: 34076936 DOI: 10.1111/nmo.14178] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 04/05/2021] [Accepted: 04/28/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND The colonic motor patterns associated with gas transit are poorly understood. This study describes the application of high-resolution impedance manometry (HRiM) in the human colon in vivo to characterize distal colonic motility and gas transit; (a) after a meal and (b) after intraluminal gas insufflation into the sigmoid colon. METHODS HRiM recordings were performed in 19 healthy volunteers, with sensors positioned from the distal descending colon to the proximal rectum. Protocol 1 (n = 10) compared pressure and impedance prior to and after a meal. Protocol 2 (n = 9) compared pressure and impedance before and after gas insufflation into the sigmoid colon (60 mL total volume). KEY RESULTS Both the meal and gas insufflation resulted in an increase in the prevalence of the 2-8/minute "cyclic motor pattern" (meal: (t(9) = -6.42, P<0.001); gas insufflation (t(8) = -3.13, P = 0.01)), and an increase in the number of antegrade and retrograde propagating impedance events (meal: Z = -2.80, P = 0.005; gas insufflation Z = -2.67, P = 0.008). Propagating impedance events temporally preceded antegrade and retrograde propagating contractions, representing a column of luminal gas being displaced ahead of a propagating contraction. Three participants reported an urge to pass flatus and/or flatus during the studies. CONCLUSIONS AND INFERENCES Initiation of the 2-8/minute cyclic motor pattern in the distal colon occurs both following a meal and/or as a localized sensorimotor response to gas. The near-absence of a flatal urge and the temporal association between propagating contractions and gas transit supports the hypothesis that the 2-8/minute cyclic motor pattern acts as a physiological "brake" modulating rectal filling.
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Affiliation(s)
- Paul T Heitmann
- College of Medicine and Public Health, Flinders University, Adelaide, Australia.,Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, Australia
| | - Reizal Mohd Rosli
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Lyn Maslen
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, Australia
| | - Lukasz Wiklendt
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Raghu Kumar
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, Australia
| | - Taher I Omari
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - David Wattchow
- College of Medicine and Public Health, Flinders University, Adelaide, Australia.,Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, Australia
| | - Marcello Costa
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Simon J Brookes
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Phil G Dinning
- College of Medicine and Public Health, Flinders University, Adelaide, Australia.,Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, Australia
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32
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Seo SHB, Carson DA, Bhat S, Varghese C, Wells CI, Bissett IP, O'Grady G. Prolonged postoperative ileus following right- versus left-sided colectomy: A systematic review and meta-analysis. Colorectal Dis 2021; 23:3113-3122. [PMID: 34714601 DOI: 10.1111/codi.15969] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 10/05/2021] [Accepted: 10/22/2021] [Indexed: 02/08/2023]
Abstract
AIM Prolonged postoperative ileus (PPOI) is a common complication following colonic surgery, and is associated with longer hospital stay, greater risk of complications and substantial cost for patients and hospitals. Some reports have recently suggested that gastrointestinal (GI) recovery varies based on the side of resection (i.e., right-sided vs. left-sided colectomy). This systematic review and meta-analysis aimed to compare GI recovery by resection side. METHODS The MEDLINE, Embase, Cochrane Library and CENTRAL databases were systematically searched for articles reporting GI recovery outcomes in adults undergoing elective right- versus left-sided colectomy (excluding with ileostomy) of any surgical approach. The primary outcome was PPOI, and secondary outcomes included time to first passage of flatus, stool and tolerance of solid diet, and postoperative complications. Subgroup analyses of laparoscopic procedures and cohorts without inflammatory bowel disease and sensitivity analysis of adjusted multivariate results were also performed. RESULTS Nine studies were identified, of which seven were included in the meta-analysis, comprising 29 068 colectomies (14 581 right-sided; 14 487 left-sided). PPOI was heterogeneously defined and was significantly more likely following right-sided compared to left-sided colectomy regardless of the surgical approach (OR 1.78, 95% CI 1.32-2.39; P < 0.01; I2 = 51%), as well as on subgroup analyses and adjusted multivariate meta-analysis. Secondary outcomes were reported in only a few small studies; hence meta-analysis did not produce reliable results. CONCLUSION Based on heterogeneous definitions, consistently higher rates of PPOI were observed following right- versus left-sided colectomy. These differences are currently unexplained and highlight the need for further research into the pathophysiology of ileus.
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Affiliation(s)
- Sean Ho Beom Seo
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Daniel A Carson
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Sameer Bhat
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Chris Varghese
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Cameron I Wells
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Ian P Bissett
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.,Department of Surgery, Auckland City Hospital, Auckland, New Zealand
| | - Greg O'Grady
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.,Department of Surgery, Auckland City Hospital, Auckland, New Zealand.,Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
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Wells CI, Bhat S, Paskaranandavadivel N, Lin AY, Vather R, Varghese C, Penfold JA, Rowbotham D, Dinning PG, Bissett IP, O'Grady G. Potential causes of the preoperative increase in the rectosigmoid cyclic motor pattern: A high-resolution manometry study. Physiol Rep 2021; 9:e15091. [PMID: 34837672 PMCID: PMC8627120 DOI: 10.14814/phy2.15091] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 09/30/2021] [Accepted: 10/09/2021] [Indexed: 12/16/2022] Open
Abstract
Background Cyclic motor patterns (CMPs) are the most common motor pattern in the distal colon. This study used high‐resolution (HR) colonic manometry to quantify trends in distal colonic motor activity before elective colonic surgery, determine the effect of a preoperative carbohydrate load, and compare this with a meal response in healthy controls. Methods Fiber‐optic HR colonic manometry (36 sensors, 1 cm intervals) was used to investigate distal colonic motor activity in 10 adult patients prior to elective colonic surgery, 6 of whom consumed a preoperative carbohydrate drink (200 kCal). Data were compared with nine healthy volunteers who underwent HR colonic manometry recordings while fasted and following a 700 kCal meal. The primary outcome was the percentage of recording occupied by CMPs, defined as propagating contractions at 2–4 cycles per minute (cpm). Secondary outcomes included amplitude, speed, and distance of propagating motor patterns. Results The occurrence of CMPs progressively increased in time periods closer to surgery (p = 0.001). Consumption of a preoperative drink resulted in significantly increased CMP occurrence (p = 0.04) and propagating distance (p = 0.04). There were no changes in amplitude or speed of propagating motor patterns during the preoperative period. The increase in activity following a preoperative drink was of similar magnitude to the colonic meal response observed in healthy controls, despite the lesser caloric nutrient load. Conclusion Distal colonic CMP increased in occurrence prior to surgery, amplified by ingestion of preoperative carbohydrate drinks. We hypothesize that anxiety, which is also known to rise with proximity to surgery, could play a contributing role.
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Affiliation(s)
- Cameron I Wells
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Sameer Bhat
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | | | - Anthony Y Lin
- Department of General Surgery, Capital and Coast District Health Board, Wellington, New Zealand
| | - Ryash Vather
- Department of Colorectal Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Chris Varghese
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - James A Penfold
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - David Rowbotham
- Department of Gastroenterology and Hepatology, Auckland District Health Board, Auckland, New Zealand
| | - Phil G Dinning
- Discipline of Human Physiology, Flinders University, Adelaide, South Australia, Australia.,Department of Gastroenterology, Flinders Medical Centre, Bedford Park, South Australia, Australia
| | - Ian P Bissett
- Department of Surgery, The University of Auckland, Auckland, New Zealand.,Department of Surgery, Auckland District Health Board, Auckland, New Zealand
| | - Greg O'Grady
- Department of Surgery, The University of Auckland, Auckland, New Zealand.,Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.,Department of Surgery, Auckland District Health Board, Auckland, New Zealand
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Huizinga JD, Hussain A, Chen JH. Interstitial cells of Cajal and human colon motility in health and disease. Am J Physiol Gastrointest Liver Physiol 2021; 321:G552-G575. [PMID: 34612070 DOI: 10.1152/ajpgi.00264.2021] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Our understanding of human colonic motility, and autonomic reflexes that generate motor patterns, has increased markedly through high-resolution manometry. Details of the motor patterns are emerging related to frequency and propagation characteristics that allow linkage to interstitial cells of Cajal (ICC) networks. In studies on colonic motor dysfunction requiring surgery, ICC are almost always abnormal or significantly reduced. However, there are still gaps in our knowledge about the role of ICC in the control of colonic motility and there is little understanding of a mechanistic link between ICC abnormalities and colonic motor dysfunction. This review will outline the various ICC networks in the human colon and their proven and likely associations with the enteric and extrinsic autonomic nervous systems. Based on our extensive knowledge of the role of ICC in the control of gastrointestinal motility of animal models and the human stomach and small intestine, we propose how ICC networks are underlying the motor patterns of the human colon. The role of ICC will be reviewed in the autonomic neural reflexes that evoke essential motor patterns for transit and defecation. Mechanisms underlying ICC injury, maintenance, and repair will be discussed. Hypotheses are formulated as to how ICC dysfunction can lead to motor abnormalities in slow transit constipation, chronic idiopathic pseudo-obstruction, Hirschsprung's disease, fecal incontinence, diverticular disease, and inflammatory conditions. Recent studies on ICC repair after injury hold promise for future therapies.
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Affiliation(s)
- Jan D Huizinga
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Amer Hussain
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Ji-Hong Chen
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
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Understanding the physiology of human defaecation and disorders of continence and evacuation. Nat Rev Gastroenterol Hepatol 2021; 18:751-769. [PMID: 34373626 DOI: 10.1038/s41575-021-00487-5] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/21/2021] [Indexed: 02/07/2023]
Abstract
The act of defaecation, although a ubiquitous human experience, requires the coordinated actions of the anorectum and colon, pelvic floor musculature, and the enteric, peripheral and central nervous systems. Defaecation is best appreciated through the description of four phases, which are, temporally and physiologically, reasonably discrete. However, given the complexity of this process, it is unsurprising that disorders of defaecation are both common and problematic; almost everyone will experience constipation at some time in their life and many will develop faecal incontinence. A detailed understanding of the normal physiology of defaecation and continence is critical to inform management of disorders of defaecation. During the past decade, there have been major advances in the investigative tools used to assess colonic and anorectal function. This Review details the current understanding of defaecation and continence. This includes an overview of the relevant anatomy and physiology, a description of the four phases of defaecation, and factors influencing defaecation (demographics, stool frequency/consistency, psychobehavioural factors, posture, circadian rhythm, dietary intake and medications). A summary of the known pathophysiology of defaecation disorders including constipation, faecal incontinence and irritable bowel syndrome is also included, as well as considerations for further research in this field.
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Lin AY, Varghese C, Du P, Wells CI, Paskaranandavadivel N, Gharibans AA, Erickson JC, Bissett IP, O'Grady G. Intraoperative serosal extracellular mapping of the human distal colon: a feasibility study. Biomed Eng Online 2021; 20:105. [PMID: 34656127 PMCID: PMC8520224 DOI: 10.1186/s12938-021-00944-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 10/05/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Cyclic motor patterns (CMP) are the predominant motor pattern in the distal colon, and are important in both health and disease. Their origin, mechanism and relation to bioelectrical slow-waves remain incompletely understood. During abdominal surgery, an increase in the CMP occurs in the distal colon. This study aimed to evaluate the feasibility of detecting propagating slow waves and spike waves in the distal human colon through intraoperative, high-resolution (HR), serosal electrical mapping. METHODS HR electrical recordings were obtained from the distal colon using validated flexible PCB arrays (6 × 16 electrodes; 4 mm inter-electrode spacing; 2.4 cm2, 0.3 mm diameter) for up to 15 min. Passive unipolar signals were obtained and analysed. RESULTS Eleven patients (33-71 years; 6 females) undergoing colorectal surgery under general anaesthesia (4 with epidurals) were recruited. After artefact removal and comprehensive manual and automated analytics, events consistent with regular propagating activity between 2 and 6 cpm were not identified in any patient. Intermittent clusters of spike-like activities lasting 10-180 s with frequencies of each cluster ranging between 24 and 42 cpm, and an average amplitude of 0.54 ± 0.37 mV were recorded. CONCLUSIONS Intraoperative colonic serosal mapping in humans is feasible, but unlike in the stomach and small bowel, revealed no regular propagating electrical activity. Although sporadic, synchronous spike-wave events were identifiable. Alternative techniques are required to characterise the mechanisms underlying the hyperactive CMP observed in the intra- and post-operative period. NEW FINDINGS The aim of this study was to assess the feasibility of detecting propagating electrical activity that may correlate to the cyclic motor pattern in the distal human colon through intraoperative, high-resolution, serosal electrical mapping. High-resolution electrical mapping of the human colon revealed no regular propagating activity, but does reveal sporadic spike-wave events. These findings indicate that further research into appropriate techniques is required to identify the mechanism of hyperactive cyclic motor pattern observed in the intra- and post-operative period in humans.
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Affiliation(s)
- Anthony Y Lin
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, 1142, Auckland, New Zealand
| | - Chris Varghese
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, 1142, Auckland, New Zealand
| | - Peng Du
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
| | - Cameron I Wells
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, 1142, Auckland, New Zealand
| | | | - Armen A Gharibans
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, 1142, Auckland, New Zealand
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
| | - Jonathan C Erickson
- Department of Physics-Engineering, Washington & Lee University, Lexington, VA, USA
| | - Ian P Bissett
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, 1142, Auckland, New Zealand
- Department of Surgery, Auckland City Hospital, Auckland, New Zealand
| | - Greg O'Grady
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, 1142, Auckland, New Zealand.
- Department of Surgery, Auckland City Hospital, Auckland, New Zealand.
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The Sphincter of O'Beirne - Part 1: Study of 18 Normal Subjects. Dig Dis Sci 2021; 66:3516-3528. [PMID: 33462748 DOI: 10.1007/s10620-020-06657-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 10/05/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Gastroenterologists have ignored or emphasized the importance of the rectosigmoid junction in continence or constipation on and off for 200 years. Here, we revisit its significance using high-resolution colonic manometry. METHODS Manometry, using an 84-channel water-perfused catheter, was performed in 18 healthy volunteers. RESULTS The rectosigmoid junction registers as an intermittent pressure band of 26.2 ± 7.2 mmHg, or intermittent phasic transient pressure increases at a dominant frequency of 3 cpm and an amplitude of 28.6 ± 8.6 mmHg; or a combination of tone and transient pressures, at a single sensor, 10-17 cm above the anal verge. Features are its relaxation or contraction in concert with relaxation or contraction of the anal sphincters when a motor pattern such as a high-amplitude propagating pressure wave or a simultaneous pressure wave comes down, indicating that such pressure increases or decreases at the rectosigmoid junction are part of neurally driven programs. We show that the junction is a site where motor patterns end, or where they start; e.g. retrogradely propagating cyclic motor patterns emerge from the junction. CONCLUSIONS The rectosigmoid junction is a functional sphincter that should be referred to as the sphincter of O'Beirne; it is part of the "braking mechanism," contributing to continence by keeping content away from the rectum. In an accompanying case report, we show that its excessive presence in a patient with severe constipation can be a primary pathophysiology.
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Chen JH, Collins SM, Milkova N, Pervez M, Nirmalathasan S, Tan W, Hanman A, Huizinga JD. The Sphincter of O'Beirne-Part 2: Report of a Case of Chronic Constipation with Autonomous Dyssynergia. Dig Dis Sci 2021; 66:3529-3541. [PMID: 33462747 DOI: 10.1007/s10620-020-06723-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 11/15/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Chronic constipation can have one or more of many etiologies, and a diagnosis based on symptoms is not sufficient as a basis for treatment, in particular surgery. AIM To investigate the cause of chronic constipation in a patient with complete absence of spontaneous bowel movements. METHODS High-resolution colonic manometry was performed to assess motor functions of the colon, rectum, the sphincter of O'Beirne and the anal sphincters. RESULTS Normal colonic motor patterns were observed, even at baseline, but a prominent high-pressure zone at the rectosigmoid junction, the sphincter of O'Beirne, was consistently present. In response to high-amplitude propagating pressure waves (HAPWs) that were not consciously perceived, the sphincter and the anal sphincters would not relax and paradoxically contract, identified as autonomous dyssynergia. Rectal bisacodyl evoked marked HAPW activity with complete relaxation of the sphincter of O'Beirne and the anal sphincters, indicating that all neural pathways to generate the coloanal reflex were intact but had low sensitivity to physiological stimuli. A retrograde propagating cyclic motor pattern initiated at the sphincter of O'Beirne, likely contributing to failure of content to move into the rectum. CONCLUSIONS Chronic constipation without the presence of spontaneous bowel movements can be associated with normal colonic motor patterns but a highly exaggerated pressure at the rectosigmoid junction: the sphincter of O'Beirne, and failure of this sphincter and the anal sphincters to relax associated with propulsive motor patterns. The sphincter of O'Beirne can be an important part of the pathophysiology of chronic constipation.
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Affiliation(s)
- Ji-Hong Chen
- Department of Medicine-Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, HSC-3H1F, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada.
| | - Stephen M Collins
- Department of Medicine-Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, HSC-3H1F, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada
| | - Natalija Milkova
- Department of Medicine-Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, HSC-3H1F, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada
| | - Maham Pervez
- Department of Medicine-Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, HSC-3H1F, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada
| | - Sharjana Nirmalathasan
- Department of Medicine-Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, HSC-3H1F, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada
| | - Wei Tan
- Department of Medicine-Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, HSC-3H1F, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada
| | - Alicia Hanman
- Department of Medicine-Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, HSC-3H1F, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada
| | - Jan D Huizinga
- Department of Medicine-Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, HSC-3H1F, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada
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Costa M, Hibberd TJ, Keightley LJ, Wiklendt L, Kyloh MA, Dinning PG, Brookes SJH, Spencer NJ. Novel intrinsic neurogenic and myogenic mechanisms underlying the formation of faecal pellets along the large intestine of guinea-pigs. J Physiol 2021; 599:4561-4579. [PMID: 34418078 DOI: 10.1113/jp282069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 08/17/2021] [Indexed: 11/08/2022] Open
Abstract
Soft faecal material is transformed into discrete, pellet-shaped faeces at the colonic flexure. Here, analysis of water content in natural faecal material revealed a decline from cecum to rectum without significant changes at the flexure. Thus, pellet formation is not explained by changes in viscosity alone. We then used video imaging of colonic wall movements with electromyography in isolated preparations containing guinea-pig proximal colon, colonic flexure and distal colon. To investigate the pellet formation process, the colonic segments were infused with artificial contents (Krebs solution and 4-6% methylcellulose) to simulate physiological faecal content flow. Remarkably, pellet formation took place in vitro, without extrinsic neural inputs. Infusion evoked slowly propagating neurogenic contractions, the proximal colon migrating motor complexes (∼0.6 cpm), which initiated pellet formation at the flexure. Lesion of the flexure, but not the proximal colon, disrupted the formation of normal individual pellets. In addition, a distinct myogenic mechanism was identified, whereby slow phasic contractions (∼1.9 cpm) initiated at the flexure and propagated short distances retrogradely into the proximal colon and antegradely into the distal colon. There were no detectable changes in the density or distribution of pacemaker-type interstitial cells of Cajal across the flexure. The findings provide new insights into how solid faecal content is generated, suggesting the major mechanisms underlying faecal pellet formation involve the unique interaction at the colonic flexure between antegrade proximal colon migrating motor complexes, organized by enteric neurons, and retrograde myogenic slow phasic contractions. Additional, as yet unidentified extrinsic and/or humoral influences appear to contribute to processing of faecal content in vivo. KEY POINTS: In herbivores, including guinea-pigs, clearly defined faecal pellets are formed at a distinct location along the large intestine (colonic flexure). The mechanism underlying the formation of these faecal pellets at this region has remained unknown. We reveal a progressive and gradual reduction in water content of faecal content along the bowel. Hence, the distinct transition from amorphous to pellet shaped faecal content could not be explained by a dramatic increase in water reabsorption from a specific site. We discovered patterns of anterograde neurogenic and retrograde myogenic motor activity that facilitate the formation of faecal pellets. The formation of 'pellet-like' boluses at the colonic flexure involves interaction of an antegrade migrating motor complex in the proximal colon and retrograde myogenic slow phasic contractions that emerge from the colonic flexure. The findings uncover intrinsic mechanisms responsible for the formation of discrete faecal scybala in the large intestine of a vertebrate.
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Affiliation(s)
- Marcello Costa
- Discipline of Human Physiology, College of Medicine and Public Health Flinders University, Adelaide, SA, Australia
| | - Timothy J Hibberd
- Discipline of Human Physiology, College of Medicine and Public Health Flinders University, Adelaide, SA, Australia
| | - Lauren J Keightley
- Discipline of Human Physiology, College of Medicine and Public Health Flinders University, Adelaide, SA, Australia
| | - Lukasz Wiklendt
- Discipline of Human Physiology, College of Medicine and Public Health Flinders University, Adelaide, SA, Australia
| | - Melinda A Kyloh
- Discipline of Human Physiology, College of Medicine and Public Health Flinders University, Adelaide, SA, Australia
| | - Phil G Dinning
- Discipline of Human Physiology, College of Medicine and Public Health Flinders University, Adelaide, SA, Australia.,Discipline of Surgery and Gastroenterology, Flinders Medical Centre, Adelaide, SA, Australia
| | - Simon J H Brookes
- Discipline of Human Physiology, College of Medicine and Public Health Flinders University, Adelaide, SA, Australia
| | - Nick J Spencer
- Discipline of Human Physiology, College of Medicine and Public Health Flinders University, Adelaide, SA, Australia
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Zhao Q, Chen YY, Xu DQ, Yue SJ, Fu RJ, Yang J, Xing LM, Tang YP. Action Mode of Gut Motility, Fluid and Electrolyte Transport in Chronic Constipation. Front Pharmacol 2021; 12:630249. [PMID: 34385914 PMCID: PMC8353128 DOI: 10.3389/fphar.2021.630249] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 06/28/2021] [Indexed: 12/12/2022] Open
Abstract
Chronic constipation is a common gastrointestinal disorder, with a worldwide incidence of 14–30%. It negatively affects quality of life and is associated with a considerable economic burden. As a disease with multiple etiologies and risk factors, it is important to understand the pathophysiology of chronic constipation. The purpose of this review is to discuss latest findings on the roles of gut motility, fluid, and electrolyte transport that contribute to chronic constipation, and the main drugs available for treating patients. We conducted searches on PubMed and Google Scholar up to 9 February 2021. MeSH keywords “constipation”, “gastrointestinal motility”, “peristalsis”, “electrolytes”, “fluid”, “aquaporins”, and “medicine” were included. The reference lists of searched articles were reviewed to identify further eligible articles. Studies focusing on opioid-induced constipation, evaluation, and clinic management of constipation were excluded. The occurrence of constipation is inherently connected to disorders of gut motility as well as fluid and electrolyte transport, which involve the nervous system, endocrine signaling, the gastrointestinal microbiota, ion channels, and aquaporins. The mechanisms of action and application of the main drugs are summarized; a better understanding of ion channels and aquaporins may be helpful for new drug development. This review aims to provide a scientific basis that can guide future research on the etiology and treatment of constipation.
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Affiliation(s)
- Qi Zhao
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, China
| | - Yan-Yan Chen
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, China
| | - Ding-Qiao Xu
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, China
| | - Shi-Jun Yue
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, China
| | - Rui-Jia Fu
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, China
| | - Jie Yang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, China
| | - Li-Ming Xing
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, China
| | - Yu-Ping Tang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi'an, China
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Wells CI, Paskaranandavadivel N, Du P, Penfold JA, Gharibans A, Bissett IP, O'Grady G. A novel mechanism for acute colonic pseudo-obstruction revealed by high-resolution manometry: A case report. Physiol Rep 2021; 9:e14950. [PMID: 34231325 PMCID: PMC8261480 DOI: 10.14814/phy2.14950] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 06/10/2021] [Accepted: 06/11/2021] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Acute colonic pseudo-obstruction (ACPO) is a severe form of colonic dysmotility and is associated with considerable morbidity. The pathophysiology of ACPO is considered to be multifactorial but has not been clarified. Although colonic motility is commonly assumed to be hypoactive, there is little direct pathophysiological evidence to support this claim. METHODS A 56-year-old woman who developed ACPO following spinal surgery underwent 24 h of continuous high-resolution colonic manometry (1 cm resolution over 36 cm) following endoscopic decompression. Manometry data were analyzed and correlated with a three-dimensional colonic model developed from computed tomography (CT) imaging. RESULTS The distal colon was found to be profoundly hyperactive, showing near-continuous non-propagating motor activity. Dominant frequencies at 2-6 and 8-12 cycles per minute were observed. The activity was often dissociated and out-of-phase across adjacent regions. The mean amplitude of motor activity was higher than that reported from pre- and post-prandial healthy controls. Correlation with CT imaging suggested that these disordered hyperactive motility sequences might act as a functional pseudo-obstruction in the distal colon resulting in secondary proximal dilatation. CONCLUSIONS This is the first detailed description of motility patterns in ACPO and suggests a novel underlying disease mechanism, warranting further investigation and identification of potential therapeutic targets.
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Affiliation(s)
- Cameron I. Wells
- Department of SurgeryFaculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
| | | | - Peng Du
- Auckland Bioengineering InstituteThe University of AucklandAucklandNew Zealand
| | - James A. Penfold
- Department of SurgeryFaculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
| | - Armen Gharibans
- Department of SurgeryFaculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
- Auckland Bioengineering InstituteThe University of AucklandAucklandNew Zealand
| | - Ian P. Bissett
- Department of SurgeryFaculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
| | - Greg O'Grady
- Department of SurgeryFaculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
- Auckland Bioengineering InstituteThe University of AucklandAucklandNew Zealand
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Dudi-Venkata NN, Kroon HM, Bedrikovetski S, Lewis M, Lawrence MJ, Hunter RA, Moore JW, Thomas ML, Sammour T. Impact of STIMUlant and osmotic LAXatives (STIMULAX trial) on gastrointestinal recovery after colorectal surgery: randomized clinical trial. Br J Surg 2021; 108:797-803. [PMID: 34136900 DOI: 10.1093/bjs/znab140] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 04/06/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Recovery of gastrointestinal (GI) function is often delayed after colorectal surgery. Enhanced recovery protocols (ERPs) recommend routine laxative use, but evidence of benefit is unclear. This study aimed to investigate whether the addition of multimodal laxatives to an ERP improves return of GI function in patients undergoing colorectal surgery. METHODS This was a single-centre, parallel, open-label RCT. All adult patients undergoing elective colorectal resection or having stoma formation or reversal at the Royal Adelaide Hospital between August 2018 and May 2020 were recruited into the study. The STIMULAX group received oral Coloxyl® with senna and macrogol, with a sodium phosphate enema in addition for right-sided operations. The control group received standard ERP postoperative care. The primary outcome was GI-2, a validated composite measure defined as the interval from surgery until first passage of stool and tolerance of solid intake for 24 h in the absence of vomiting. Secondary outcomes were the incidence of prolonged postoperative ileus (POI), duration of hospital stay, and postoperative complications. The analysis was performed on an intention-to-treat basis. RESULTS Of a total of 170 participants, 85 were randomized to each group. Median GI-2 was 1 day shorter in the STIMULAX compared with the control group (median 2 (i.q.r. 1.5-4) versus 3 (2-5.5) days; 95 per cent c.i. -1 to 0 days; P = 0.029). The incidence of prolonged POI was lower in the STIMULAX group (22 versus 38 per cent; relative risk reduction 42 per cent; P = 0.030). There was no difference in duration of hospital day or 30-day postoperative complications (including anastomotic leak) between the STIMULAX and control groups. CONCLUSION Routine postoperative use of multimodal laxatives after elective colorectal surgery results in earlier recovery of gastrointestinal function and reduces the incidence of prolonged POI. Registration number: ACTRN12618001261202 (www.anzctr.org.au).
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Affiliation(s)
- N N Dudi-Venkata
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia.,Discipline of Surgery, Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia
| | - H M Kroon
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia.,Discipline of Surgery, Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia
| | - S Bedrikovetski
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia.,Discipline of Surgery, Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia
| | - M Lewis
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - M J Lawrence
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - R A Hunter
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - J W Moore
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia.,Discipline of Surgery, Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia
| | - M L Thomas
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia.,Discipline of Surgery, Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia
| | - T Sammour
- Colorectal Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia.,Discipline of Surgery, Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia
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43
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Huizinga JD, Pervez M, Nirmalathasan S, Chen JH. Characterization of haustral activity in the human colon. Am J Physiol Gastrointest Liver Physiol 2021; 320:G1067-G1080. [PMID: 33909507 DOI: 10.1152/ajpgi.00063.2021] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Contraction patterns of the human colon are rarely discussed from the perspective of its haustra. Colonic motility was analyzed in 21 healthy subjects using 84-sensor manometry catheters with 1-cm sensor spacing. Capsule endoscopy and manometry showed evidence of narrow rhythmic circular muscle contractions. X-ray images of haustra and sensor locations allowed us to identify manometry motor activity as intrahaustral activity. Two common motor patterns were observed that we infer to be associated with individual haustra: rhythmic pressure activity confined to a single sensor, and activity confined to a section of the colon of 3-6 cm length. Intrahaustral activity was observed by 3-4 sensors. Approximately 50% of the haustra were intermittently active for ∼30% of the time; 2,402 periods of haustral activity were analyzed. Intrahaustral activity showed rhythmic pressure waves, propagating in mixed direction, 5-30 mmHg in amplitude at a frequency of ∼3 cpm (range 2-6) or ∼12 cpm (range 7-15), or exhibiting a checkerboard segmentation pattern. Boundaries of the haustra showed rhythmic pressure activity with or without elevated baseline pressure. Active haustra often showed no boundary activity probably allowing transit to neighboring haustra. Haustral boundaries were seen at the same sensor for the 6- to 8-h study duration, indicating that they did not propagate, thereby likely contributing to continence. The present study elucidates the motility characteristics of haustral boundaries and the nature of intrahaustral motor patterns and paves the way for investigating their possible role in pathophysiology of defecation disorders.NEW & NOTEWORTHY Here, we present the first full characterization and quantification of motor patterns that we infer to be confined to single haustra, both intrahaustral activity and haustral boundary activity, in the human colon using high-resolution manometry. Haustral activity is intermittent but consistently present in about half of the haustra. Intrahaustral activity presents as a cyclic motor pattern of mixed propagation direction dominated by simultaneous pressure waves that can resolve into checkerboard segmentation, allowing for mixing, absorption, and stool formation.
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Affiliation(s)
- Jan D Huizinga
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Maham Pervez
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Sharjana Nirmalathasan
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Ji-Hong Chen
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
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High-Resolution Colonic Manometry Pressure Profiles Are Similar in Asymptomatic Diverticulosis and Controls. Dig Dis Sci 2021; 66:832-842. [PMID: 32399665 DOI: 10.1007/s10620-020-06320-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 05/02/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Elevated colonic pressures and increased colonic activity have been thought to contribute to the pathophysiology of diverticulosis. However, evidence for this has been limited to low-resolution manometry, which is of limited accuracy. AIMS This study aimed to evaluate the contraction pressures, counts, and distance of propagation recorded by high-resolution colonic manometry in diverticulosis vs control patients. METHODS High-resolution colonic manometry was used to record descending and sigmoid colon activity pre- and post-meal in patients with established, asymptomatic diverticulosis and in healthy controls. Antegrade and retrograde propagating contractions, distance of propagation (mm), and mean contraction pressures (mmHg) in the descending and sigmoid colon were compared between patients and controls for all isolated propagating contractions, the cyclic motor pattern, and high-amplitude propagating contractions independently. RESULTS Mean manometry pressures were not different between controls and diverticulosis patients (p > 0.05 for all comparisons). In the descending colon, diverticulosis patients had lower post-meal mean distance of propagation for all propagating contractions [10.8 (SE1.5) mm vs 20.0 (2.0) mm, p = 0.003] and the cyclic motor pattern [6.0 (2.5) mm vs 17.1 (2.8) mm, p = 0.01]. In the sigmoid colon, diverticulosis patients showed lower post-meal mean distance of propagation for all propagating contractions [10.8 (1.5) mm vs 20.2 (5.9) mm, p = 0.01] and a lower post-meal increase in retrograde propagating contractions (p = 0.04). CONCLUSIONS In this first high-resolution colonic manometry study of patients with diverticular disease, we did not find evidence for increased manometric pressures or increased colonic activity in patients with diverticular disease.
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Seo SHB, Bissett I, O’Grady G. Variable Gut Function Recovery After Right vs. Left Colectomy May Be Due to Rectosigmoid Hyperactivity. Front Physiol 2021; 12:635167. [PMID: 33708140 PMCID: PMC7940204 DOI: 10.3389/fphys.2021.635167] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 01/19/2021] [Indexed: 12/11/2022] Open
Abstract
It is established that gut function recovers slower after right vs. left colectomies with higher rates of prolonged post-operative ileus (PPOI), but the reason is unclear. Development of PPOI is multifactorial. A recent manometry study in right colectomy patients showed that the distal colon becomes hyperactive after surgery with predominantly cyclic motor patterns (CMPs). In this perspective, we evaluate the hypothesis that the slower gut recovery after right hemicolectomy could be induced by a functional obstruction due to hyperactive CMPs.
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Affiliation(s)
- Sean Ho Beom Seo
- Department of Surgery, University of Auckland, Auckland, New Zealand
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46
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Wiklendt L, Costa M, Scott MS, Brookes SJH, Dinning PG. Automated Analysis Using a Bayesian Functional Mixed-Effects Model With Gaussian Process Responses for Wavelet Spectra of Spatiotemporal Colonic Manometry Signals. Front Physiol 2021; 11:605066. [PMID: 33643057 PMCID: PMC7905106 DOI: 10.3389/fphys.2020.605066] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 12/16/2020] [Indexed: 12/22/2022] Open
Abstract
Manual analysis of human high-resolution colonic manometry data is time consuming, non-standardized and subject to laboratory bias. In this article we present a technique for spectral analysis and statistical inference of quasiperiodic spatiotemporal signals recorded during colonic manometry procedures. Spectral analysis is achieved by computing the continuous wavelet transform and cross-wavelet transform of these signals. Statistical inference is achieved by modeling the resulting time-averaged amplitudes in the frequency and frequency-phase domains as Gaussian processes over a regular grid, under the influence of categorical and numerical predictors specified by the experimental design as a functional mixed-effects model. Parameters of the model are inferred with Hamiltonian Monte Carlo. Using this method, we re-analyzed our previously published colonic manometry data, comparing healthy controls and patients with slow transit constipation. The output from our automated method, supports and adds to our previous manual analysis. To obtain these results took less than two days. In comparison the manual analysis took 5 weeks. The proposed mixed-effects model approach described here can also be used to gain an appreciation of cyclical activity in individual subjects during control periods and in response to any form of intervention.
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Affiliation(s)
- Lukasz Wiklendt
- College of Medicine and Public Health, Centre for Neuroscience, Flinders University, Bedford Park, SA, Australia
| | - Marcello Costa
- College of Medicine and Public Health, Centre for Neuroscience, Flinders University, Bedford Park, SA, Australia
| | - Mark S. Scott
- Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Queen Mary University of London, London, United Kingdom
| | - Simon J. H. Brookes
- College of Medicine and Public Health, Centre for Neuroscience, Flinders University, Bedford Park, SA, Australia
| | - Phil G. Dinning
- College of Medicine and Public Health, Centre for Neuroscience, Flinders University, Bedford Park, SA, Australia
- Discipline of Surgery and Gastroenterology, Flinders Medical Centre, Bedford Park, SA, Australia
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47
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Keane C, Paskaranandavadivel N, Vather R, Rowbotham D, Arkwright J, Dinning P, Bissett I, O'Grady G. Altered colonic motility is associated with low anterior resection syndrome. Colorectal Dis 2021; 23:415-423. [PMID: 33253472 DOI: 10.1111/codi.15465] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 10/13/2020] [Accepted: 11/17/2020] [Indexed: 12/15/2022]
Abstract
AIM Patients frequently suffer from low anterior resection syndrome (LARS) after distal colorectal resection. The pathophysiology of LARS has not been clearly elucidated. We hypothesized that rectosigmoid resection could impair motility patterns in the distal colon, such as the rectosigmoid brake, which contribute to control of stool form and frequency. METHOD High-resolution colonic manometry was performed in patients who had previously undergone distal colorectal resection (mean 6.8 years after resection) and non-operative controls before and after a standardized meal. Symptoms were assessed using the LARS score. Propagating contractions were compared between patients with and without LARS, and controls. RESULTS Data were analysed from 23 patients (11 no-LARS; 12 LARS) and nine controls. All groups demonstrated a significant meal response. LARS patients had fewer post-prandial antegrade propagating contractions than controls (P = 0.028), and fewer retrograde propagating contractions both pre- (P = 0.005) and post-prandially (P = 0.004). Post-prandially, the LARS group had a significantly lower percentage of propagating contractions that met the criteria for the cyclic motor pattern compared to the control group (26% vs. 58%; P = 0.009). There were significant differences in antegrade and retrograde amplitude (P = 0.049; P = 0.018) and distance of propagation (P = 0.003; P = 0.002) post-prandially between LARS patients and controls. CONCLUSION Rectosigmoid resection alters the meal response following anterior resection, including impairment of the rectosigmoid brake cyclic motor pattern. These findings help to quantify the impaired functional motility after rectosigmoid resection and offer new insights into the mechanisms of LARS.
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Affiliation(s)
- Celia Keane
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | | | - Ryash Vather
- Colorectal Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - David Rowbotham
- Department of Gastroenterology, Auckland City Hospital, Auckland, New Zealand
| | - John Arkwright
- College of Science and Engineering, Flinders University, Adelaide, South Australia, Australia
| | - Phil Dinning
- Department of Surgery and Gastroenterology, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia
| | - Ian Bissett
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Greg O'Grady
- Department of Surgery, University of Auckland, Auckland, New Zealand
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48
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Paskaranandavadivel N, Lin AY, Cheng LK, Bissett I, Lowe A, Arkwright J, Mollaee S, Dinning PG, O'Grady G. ManoMap: an automated system for characterization of colonic propagating contractions recorded by high-resolution manometry. Med Biol Eng Comput 2021; 59:417-429. [PMID: 33496911 DOI: 10.1007/s11517-021-02316-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Accepted: 01/15/2021] [Indexed: 11/30/2022]
Abstract
RATIONALE Colonic high-resolution manometry (cHRM) is an emerging clinical tool for defining colonic function in health and disease. Current analysis methods are conducted manually, thus being inefficient and open to interpretation bias. OBJECTIVE The main objective of the study was to build an automated system to identify propagating contractions and compare the performance to manual marking analysis. METHODS cHRM recordings were performed on 5 healthy subjects, 3 subjects with diarrhea-predominant irritable bowel syndrome, and 3 subjects with slow transit constipation. Two experts manually identified propagating contractions, from five randomly selected 10-min segments from each of the 11 subjects (72 channels per dataset, total duration 550 min). An automated signal processing and detection platform was developed to compare its effectiveness to manually identified propagating contractions. In the algorithm, individual pressure events over a threshold were identified and were then grouped into a propagating contraction. The detection platform allowed user-selectable thresholds, and a range of pressure thresholds was evaluated (2 to 20 mmHg). KEY RESULTS The automated system was found to be reliable and accurate for analyzing cHRM with a threshold of 15 mmHg, resulting in a positive predictive value of 75%. For 5-h cHRM recordings, the automated method takes 22 ± 2 s for analysis, while manual identification would take many hours. CONCLUSIONS An automated framework was developed to filter, detect, quantify, and visualize propagating contractions in cHRM recordings in an efficient manner that is reliable and consistent.
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Affiliation(s)
- Niranchan Paskaranandavadivel
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
- Department of Surgery, University of Auckland, Auckland, New Zealand.
| | - Anthony Y Lin
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Leo K Cheng
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand
- Vanderbilt University, Nashville, TN, USA
| | - Ian Bissett
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Auckland City Hospital, Auckland, New Zealand
| | - Andrew Lowe
- Institute of Biomedical Engineering, Auckland University of Technology, Auckland, New Zealand
| | - John Arkwright
- College of Science and Engineering, Flinders University, Adelaide, Australia
| | - Saeed Mollaee
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand
| | - Phil G Dinning
- Departments of Gastroenterology & Surgery Flinders Medical Centre, Flinders University, Adelaide, Australia
| | - Gregory O'Grady
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Auckland City Hospital, Auckland, New Zealand
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49
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Bassotti G. 1907-2020: more than one century of colonic mass movements in humans. Am J Physiol Gastrointest Liver Physiol 2021; 320:G117-G124. [PMID: 33174455 DOI: 10.1152/ajpgi.00375.2020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Motility of the large bowel may be grossly subdivided in two types of contractile activity: low-amplitude single or cyclic propagated waves and high-amplitude propagated activity. The latter is mainly apt to shift relatively large amounts of colonic contents, and it is related to defecation. The main component of this propagated activity is represented by the radiologically identified mass movements that have a manometric equivalent known as high-amplitude propagated contractions (HAPC). The present article reviews origins and characterization of HAPC in the time course of colonic motility investigations, and correlates it with technological advancements in recent years, putting into perspective the future possible options to better detect and investigate these important physiological events.
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Affiliation(s)
- Gabrio Bassotti
- Gastroenterology, Hepatology and Digestive Endoscopy Section, Department of Medicine, University of Perugia School of Medicine, Perugia, Italy.,Gastroenterology and Hepatology Unit, Santa Maria della Misericordia Hospital, Perugia, Italy
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50
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Mohd RR, Heitmann P, Raghu K, Hibbard TJ, Costa M, Wiklendt L, Wattchow DA, Arkwright J, de Fontgalland D, Brookes S, Spencer NJ, Dinning P. Distinct patterns of myogenic motor activity identified in isolated human distal colon with high-resolution manometry. Neurogastroenterol Motil 2020; 32:e13871. [PMID: 32374068 PMCID: PMC7529858 DOI: 10.1111/nmo.13871] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 03/30/2020] [Accepted: 04/13/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Colonic high-resolution manometry (HRM) has been used to reveal discrete, propagating colonic motor patterns. To help determine mechanisms underlying these patterns, we used HRM to record contractile activity in human distal colon ex vivo. METHODS Surgically excised segments of descending (n = 30) or sigmoid colon (n = 4) were immersed in oxygenated Krebs solution at 36°C (n = 34; 16 female; 67.6 ± 12.4 years; length: 24.7 ± 3.5 cm). Contractility was recorded by HRM catheters. After 30 minutes of baseline recording, 0.3 mM lidocaine and/or 1 mM hexamethonium were applied. Ascending neural pathways were activated by electrical field stimulation (EFS; 10 Hz, 0.5 ms, 50 V, 5-s duration) applied to the anal end before and after drug application. RESULTS Spontaneous propagating contractions were recorded in all specimens (0.1-1.5 cycles/minute). Most contractions occurred synchronously across all recording sites. In five specimens, rhythmic antegrade contractions propagated across the full length of the preparation. EFS evoked local contractions at the site of stimulation (latency: 5.5 ± 2.4 seconds) with greater amplitude than spontaneous contractions (EFS; 29.3 ± 26.9 vs 12.1 ± 14.8 mm Hg; P = .02). Synchronous or retrograde propagating motor patterns followed EFS; 71% spanned the entire preparation length. Hexamethonium and lidocaine modestly and only temporarily inhibited spontaneous contractions, whereas TTX increased the frequency of contractile activity while inhibiting EFS-evoked contractions. CONCLUSIONS AND INFERENCES Our study suggests that the propagated contractions recorded in the organ bath have a myogenic origin which can be regulated by neural input. Once activated at a local site, the contractions do not require the propulsion of fecal content to sustain long-distance propagation.
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Affiliation(s)
- Rosli R Mohd
- College of Medicine and Public Health & Centre for Neuroscience, Flinders University
| | - P.T Heitmann
- College of Medicine and Public Health & Centre for Neuroscience, Flinders University,Discipline of Surgery and Gastroenterology, Flinders Medical Centre, South Australia
| | - K Raghu
- Discipline of Surgery and Gastroenterology, Flinders Medical Centre, South Australia
| | - T. J. Hibbard
- College of Medicine and Public Health & Centre for Neuroscience, Flinders University
| | - M Costa
- College of Medicine and Public Health & Centre for Neuroscience, Flinders University
| | - L Wiklendt
- College of Medicine and Public Health & Centre for Neuroscience, Flinders University
| | - D. A Wattchow
- College of Medicine and Public Health & Centre for Neuroscience, Flinders University,Discipline of Surgery and Gastroenterology, Flinders Medical Centre, South Australia
| | - J Arkwright
- College of Science and Engineering, Flinders University. Adelaide, Australia
| | - D de Fontgalland
- Discipline of Surgery and Gastroenterology, Flinders Medical Centre, South Australia
| | - S.J.H Brookes
- College of Medicine and Public Health & Centre for Neuroscience, Flinders University
| | - N. J Spencer
- College of Medicine and Public Health & Centre for Neuroscience, Flinders University
| | - P.G Dinning
- College of Medicine and Public Health & Centre for Neuroscience, Flinders University,Discipline of Surgery and Gastroenterology, Flinders Medical Centre, South Australia
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