Effects of corticotropin-releasing hormone on gastric electrical activity and sensorimotor function in healthy volunteers: a double-blinded crossover study.

Biopsychosocial factors are associated with disorders of gut-brain interaction (DGBI) and exacerbate gastrointestinal symptoms. The mechanisms underlying pathophysiological alterations of stress remain unclear. Corticotropin-releasing hormone (CRH) is a central regulator of the hormonal stress response and has diverse impact on different organ systems. The aim of the present study was to investigate the effects of peripheral CRH infusion on meal-related gastrointestinal symptoms, gastric electrical activity, and gastric sensorimotor function in healthy volunteers (HVs). In a randomized, double-blinded, placebo-controlled, crossover study, we evaluated the effects of CRH on gastric motility and sensitivity. HVs were randomized to receive either peripheral-administered CRH (100 µg bolus + 1 µg/kg/h) or placebo (saline), followed by at least a 7-day washout period and assignment to the opposite treatment. Tests encompassed saliva samples, gastric-emptying (GE) testing, body surface gastric mapping (BSGM, Gastric Alimetry; Alimetry) to assess gastric myoelectrical activity with real-time symptom profiling, and a gastric barostat study to assess gastric sensitivity to distention and accommodation. Twenty HVs [13 women, mean age 29.2 ± 5.3 yr, body mass index (BMI) 23.3 ± 3.8 kg/m2] completed GE tests, of which 18 also underwent BSGM measurements during the GE tests. The GE half-time decreased significantly after CRH exposure (65.2 ± 17.4 vs. 78.8 ± 24.5 min, P = 0.02) with significantly increased gastric amplitude [49.7 (34.7-55.6) vs. 31.7 (25.7-51.0) µV, P < 0.01], saliva cortisol levels, and postprandial symptom severity. Eleven HVs also underwent gastric barostat studies on a separate day. However, the thresholds for discomfort during isobaric distensions, gastric compliance, and accommodation did not differ between CRH and placebo.NEW & NOTEWORTHY In healthy volunteers, peripheral corticotropin-releasing hormone (CRH) infusion accelerates gastric-emptying rate and increases postprandial gastric response, accompanied by a rise in symptoms, but does not alter gastric sensitivity or meal-induced accommodation. These findings underscore a significant link between stress and dyspeptic symptoms, with CRH playing a pivotal role in mediating these effects.

Effect of menstrual cycle and menopause on human gastric electrophysiology.

Chronic gastroduodenal symptoms disproportionately affect females of childbearing age; however, the effect of menstrual cycling on gastric electrophysiology is poorly defined. To establish the effect of the menstrual cycle on gastric electrophysiology, healthy subjects underwent noninvasive Body Surface Gastric Mapping (BSGM; 8x8 array) with the validated symptom logging App (Gastric Alimetry, New Zealand). Participants included were premenopausal females in follicular (n = 26) and luteal phases (n = 18) and postmenopausal females (n = 30) and males (n = 51) were controls. Principal gastric frequency (PGF), body mass index (BMI) adjusted amplitude, Gastric Alimetry Rhythm Index (GA-RI), Fed:Fasted Amplitude Ratio (ff-AR), meal response curves, and symptom burden were analyzed. Menstrual cycle-related electrophysiological changes were then transferred to an established anatomically accurate computational gastric fluid dynamics model (meal viscosity 0.1 Pas) to predict the impact on gastric mixing and emptying. PGF was significantly higher in the luteal versus follicular phase [mean 3.21 cpm, SD (0.17) vs. 2.94 cpm, SD (0.17), P < 0.001] and versus males [3.01 cpm, SD (0.2), P < 0.001]. In the computational model, this translated to 8.1% higher gastric mixing strength and 5.3% faster gastric emptying for luteal versus follicular phases. Postmenopausal females also exhibited higher PGF than females in the follicular phase [3.10 cpm, SD (0.24) vs. 2.94 cpm, SD (0.17), P = 0.01], and higher BMI-adjusted amplitude [40.7 µV (33.02-52.58) vs. 29.6 µV (26.15-39.65), P < 0.001], GA-RI [0.60 (0.48-0.73) vs. 0.43 (0.30-0.60), P = 0.005], and ff-AR [2.51 (1.79-3.47) vs. 1.48 (1.21-2.17), P = 0.001] than males. There were no differences in symptoms. These results define variations in gastric electrophysiology with regard to human menstrual cycling and menopause.NEW & NOTEWORTHY This study evaluates gastric electrophysiology in relation to the menstrual cycle using a novel noninvasive high-resolution methodology, revealing substantial variations in gastric activity with menstrual cycling and menopause. Gastric slow-wave frequency is significantly higher in the luteal versus follicular menstrual phase. Computational modeling predicts that this difference translates to higher rates of gastric mixing and liquid emptying in the luteal phase, which is consistent with previous experimental data evaluating menstrual cycling effects on gastric emptying.

Gastric Alimetry Expands Patient Phenotyping in Gastroduodenal Disorders Compared with Gastric Emptying Scintigraphy.

INTRODUCTION: Gastric emptying testing (GET) assesses gastric motility, however, is nonspecific and insensitive for neuromuscular disorders. Gastric Alimetry (GA) is a new medical device combining noninvasive gastric electrophysiological mapping and validated symptom profiling. This study assessed patient-specific phenotyping using GA compared with GET. METHODS: Patients with chronic gastroduodenal symptoms underwent simultaneous GET and GA, comprising a 30-minute baseline, 99m TC-labelled egg meal, and 4-hour postprandial recording. Results were referenced to normative ranges. Symptoms were profiled in the validated GA App and phenotyped using rule-based criteria based on their relationships to the meal and gastric activity: (i) sensorimotor, (ii) continuous, and (iii) other. RESULTS: Seventy-five patients were assessed, 77% female. Motility abnormality detection rates were as follows: GET 22.7% (14 delayed, 3 rapid), GA spectral analysis 33.3% (14 low rhythm stability/low amplitude, 5 high amplitude, and 6 abnormal frequency), and combined yield 42.7%. In patients with normal spectral analysis, GA symptom phenotypes included sensorimotor 17% (where symptoms strongly paired with gastric amplitude, median r = 0.61), continuous 30%, and other 53%. GA phenotypes showed superior correlations with Gastroparesis Cardinal Symptom Index, Patient Assessment of Upper Gastrointestinal Symptom Severity Index, and anxiety scales, whereas Rome IV Criteria did not correlate with psychometric scores ( P > 0.05). Delayed emptying was not predictive of specific GA phenotypes. DISCUSSION: GA improves patient phenotyping in chronic gastroduodenal disorders in the presence and absence of motility abnormalities with increased correlation with symptoms and psychometrics compared with gastric emptying status and Rome IV criteria. These findings have implications for the diagnostic profiling and personalized management of gastroduodenal disorders.

Risk prediction algorithms for prolonged postoperative ileus: A systematic review.

AIM: Prolonged postoperative ileus (PPOI) is common and is associated with a significant healthcare burden. Previous studies have attempted to predict PPOI clinically using risk prediction algorithms. The aim of this work was to systematically review and compare risk prediction algorithms for PPOI following colorectal surgery. METHOD: A systematic literature search was conducted using MEDLINE, Embase, Web of Science and CINAHL Plus. Studies that developed and/or validated a risk prediction algorithm for PPOI in adults following colorectal surgery were included. Data were collected on study design, population and operative characteristics, the definition of PPOI used and risk prediction algorithm design and performance. Quality appraisal was assessed using the PROBAST tool. RESULTS: Eleven studies with 87 549 participants were included in our review. Most were retrospective, single-centre analyses (6/11, 55%) and rates of PPOI varied from 10% to 28%. The most commonly used variables were sex (8/11, 73%), age (6/11, 55%) and surgical approach (5/11, 45%). Area under the curve ranged from 0.68-0.78, and only three models were validated. However, there was significant variation in the definition of PPOI used. No study reported sensitivity, specificity or positive/negative predictive values. CONCLUSION: Currently available risk prediction algorithms for PPOI appear to discriminate moderately well, although there is a lack of validation data. Future studies should aim to use a standardized definition of PPOI, comprehensively report model performance and validate their findings using internal and external methodologies.

Inhibited postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome.

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.

"Failure to Rescue" following Colorectal Cancer Resection: Variation and Improvements in a National Study of Postoperative Mortality.

OBJECTIVE: To examine variation in "failure to rescue" (FTR) as a driver of differences in mortality between centres and over time for patients undergoing colorectal cancer surgery. BACKGROUND: Wide variation exists in postoperative mortality following colorectal cancer surgery. FTR has been identified as an important determinant of variation in postoperative outcomes. We hypothesized that differences in mortality both between hospitals and over time are driven by variation in FTR. METHODS: A national population-based study of patients undergoing colorectal cancer resection from 2010 to 2019 in Aotearoa New Zealand was conducted. Rates of 90-day FTR, mortality, and complications were calculated overall, and for surgical and nonoperative complications. Twenty District Health Boards (DHBs) were ranked into quartiles using risk- and reliability-adjusted 90-day mortality rates. Variation between DHBs and trends over the 10-year period were examined. RESULTS: Overall, 15,686 patients undergoing resection for colorectal adenocarcinoma were included. Increased postoperative mortality at high-mortality centers (OR 2.4, 95% CI 1.8-3.3) was driven by higher rates of FTR (OR 2.0, 95% CI 1.5-2.8), and postoperative complications (OR 1.4, 95% CI 1.3-1.6). These trends were consistent across operative and nonoperative complications. Over the 2010 to 2019 period, postoperative mortality halved (OR 0.5, 95% CI 0.4-0.6), associated with a greater improvement in FTR (OR 0.5, 95% CI 0.4-0.7) than complications (OR 0.8, 95% CI 0.8-0.9). Differences between centers and over time remained when only analyzing patients undergoing elective surgery. CONCLUSION: Mortality following colorectal cancer resection has halved over the past decade, predominantly driven by improvements in "rescue" from complications. Differences in FTR also drive hospital-level variation in mortality, highlighting the central importance of "rescue" as a target for surgical quality improvement.

Hyperactive Distal Colonic Motility and Recovery Patterns Following Right Colectomy: A High-Resolution Manometry Study.

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 ).

Clinical utility of trans-sacral magnetic stimulation-evoked sphincter potentials and high-density electromyography in pelvic floor assessment: Technical evaluation.

AIM: Faecal incontinence is common and of multifactorial aetiologies, yet current diagnostic tools are unable to assess nerve and sphincter function objectively. We developed an anorectal high-density electromyography (HD-EMG) probe to evaluate motor-evoked potentials induced via trans-sacral magnetic stimulation (TSMS). METHOD: Anorectal probes with an 8 × 8 array of electrodes spaced 1 cm apart were developed for recording HD-EMG of the external anal sphincter. These HD-EMG probes were used to map MEP amplitudes and latencies evoked via TSMS delivered through the Magstim Rapid2 (MagStim Company). Patients undergoing pelvic floor investigations were recruited for this IDEAL Stage 2a pilot study. RESULTS: Eight participants (median age 49 years; five female) were recruited. Methodological viability, safety and diagnostic workflow were established. The test was well tolerated with median discomfort scores ≤2.5/10, median pain scores ≤1/10 and no adverse events. Higher Faecal Incontinence Severity Index scores correlated with longer MEP latencies (r = 0.58, p < 0.001) and lower MEP amplitudes (r = -0.32, p = 0.046), as did St. Mark's Incontinence Scores with both MEP latencies (r = 0.49, p = 0.001) and MEP amplitudes (r = -0.47, p = 0.002). CONCLUSION: This HD-EMG probe in conjunction with TSMS presents a novel diagnostic tool for anorectal function assessment. Spatiotemporal assessment of magnetically stimulated MEPs correlated well with symptoms and offers a feasible, safe and patient-tolerable method of evaluating pudendal nerve and external anal sphincter function. Further clinical development and evaluation of these techniques is justified.

The Longitudinal Course of Low-anterior Resection Syndrome: An individual Patient Meta-analysis.

OBJECTIVE: We aimed to better understand the longitudinal course of low anterior resection syndrome (LARS) to guide patient expectations and identify those at risk of persisting dysfunction. SUMMARY BACKGROUND DATA: LARS describes disordered bowel function after rectal resection that significantly impacts quality of life. METHODS: MEDLINE, EMBASE, CENTRAL, and CINAHL databases were systematically searched for studies that enrolled adults undergoing anterior resection for rectal cancer and used the LARS score to assess bowel function at ≥2 postoperative time points. Regression analyses were performed on deidentified patient-level data to identify predictors of change in LARS score from baseline (3-6months) to 12-months and 18-24 months. RESULTS: Eight studies with a total of 701 eligible patients were included. The mean LARS score improved over time, from 29.4 (95% confidence interval 28.6-30.1) at baseline to 16.6 at 36 months (95% confidence interval 14.2%-18.9%). On multivariable analysis, a greater improvement in mean LARS score between baseline and 12 months was associated with no ileostomy formation [mean difference (MD) -1.7 vs 1.7, P < 0.001], and presence of LARS (major vs minor vs no LARS) at baseline (MD -3.8 vs -1.7 vs 5.4, P < 0.001). Greater improvement in mean LARS score between baseline and 18-24 months was associated with partial mesorectal excision vs total mesorectal excision (MD-8.6 vs 1.5, P < 0.001) and presence of LARS (major vs minor vs no LARS) at baseline (MD -8.8 vs -5.3 vs 3.4, P < 0.001). CONCLUSIONS: LARS improves by 18 months postoperatively then remains stable for up to 3 years. Total mesorectal excision, neoadjuvant radiotherapy, and ileostomy formation negatively impact upon bowel function recovery.

Effect of prucalopride to improve time to gut function recovery following elective colorectal surgery: randomized clinical trial.

BACKGROUND: Delayed return to gut function and prolonged postoperative ileus (PPOI) delay recovery after colorectal surgery. Prucalopride is a selective serotonin-4-receptor agonist that may improve gut motility. METHODS: This was a multicentre, double-blind, parallel, placebo-controlled randomized trial of 2 mg prucalopride versus placebo in patients undergoing elective colorectal resection. Patients with inflammatory bowel disease and planned ileostomy formation were excluded, but colostomy formation was allowed. The study medication was given 2 h before surgery and daily for up to 6 days after operation. The aim was to determine whether prucalopride improved return of gut function and reduced the incidence of PPOI. The primary endpoint was time to passage of stool and tolerance of diet (GI-2). Participants were allocated in a 1 : 1 ratio, in blocks of 10. Randomization was computer-generated. All study personnel, medical staff, and patients were blinded. RESULTS: This study was completed between October 2017 and May 2020 at two tertiary hospitals in New Zealand. A total of 148 patients were randomized, 74 per arm. Demographic data were similar in the two groups. There was no difference in median time to GI-2 between prucalopride and placebo groups: 3.5 (i.q.r. 2-5) versus 4 (3-5) days respectively (P = 0.124). Prucalopride improved the median time to passage of stool (3 versus 4 days; P = 0.027) but not time to tolerance of diet (2 versus 2 days; P = 0.669) or median duration of hospital stay (4 versus 4 days; P = 0.929). In patients who underwent laparoscopic surgery (125, 84.5 per cent), prucalopride improved median time to GI-2: 3 (2-4) days versus 4 (3-5) days for placebo (P = 0.012). The rate of PPOI, complications, and adverse events was similar in the two groups. CONCLUSION: Prucalopride did not improve time to overall recovery of gut function after elective colorectal surgery. Registration number: NCT02947269 (http://www.clinicaltrials.gov).

A multi-parameter approach to measurement of spontaneous myogenic contractions in human stomach: Utilization to assess potential modulators of myogenic contractions.

Electrical slow waves, generated by interstitial cells of Cajal (ICC), cause spontaneous contractions of human stomach. Software was developed to measure muscle tone and eleven different parameters defining these contractions in human stomach, displaying data as radar plots. A pilot study assessed the effects of potential modulators, selected from among compounds known to influence ICC activity; n = 4-7 each concentration tested/compound. Human distal stomach (corpus-antrum) muscle strips were suspended in tissue baths for measuring myogenic (non-neuronal) contractions in the presence of tetrodotoxin (10-6 M). Initial characterization: Contractions (amplitude 4 ± 0.4mN, frequency 3 ± 0.1 min-1, n = 49) were unchanged by ꭃ-conotoxin GVIA (10-7 M) or indomethacin (10-6 M) but abolished by nifedipine (10-4 M). Carbachol (10-7 M) increased contraction rate and amplitude; 10-6-10-5 M increased tone and caused large, irregular contractions. [Ca2+]imodulators: Ryanodine (10-5-10-4 M) increased muscle tone accompanied by inhibition of myogenic contractions. Xestospongin-C (10-6 M; IP3 channel inhibitor) had no effects. SERCA pump inhibitors, 2-APB and cycloplazonic acid (10-5-10-4 M) increased tone and myogenic contraction amplitude before abolishing contractions; thapsigargin was weakly active. CaCC blockers: MONNA and CaCCinh-A01 had little-or-no effects on tone but reduced myogenic contractions; MONNA (10-4 M) was more effective, reducing amplitude (77.8 ± 15.2%) and frequency. CaV3.1/3.2/3.3 channel block: Mibefradil reduced tone and myogenic contraction amplitude (pIC50 4.8 ± 0.9). Inward-rectifying K+-channel inhibitor: E-4031 (10-4 M) increased contraction duration (17.4 ± 5.8%). Conclusions: (1) Measurement of multiple parameters of myogenic contractions identified subtle differences between compounds, (2) only E-4031 and CaCC blockers influenced myogenic contractions, not muscle tone, (3) studies are needed with compounds with known and/or improved selectivity/potency for human targets affecting ICC functions.

Functional Outcome of Laparoscopic-Assisted Resection Versus Open Resection of Rectal Cancer: A Secondary Analysis of the Australasian Laparoscopic Cancer of the Rectum Trial.

BACKGROUND: Low anterior resection syndrome has a significant impact on the quality of life in rectal cancer survivors. Previous studies comparing laparoscopic to open rectal resection have neglected bowel function outcomes. OBJECTIVE: This study aimed to assess whether there is a difference in the functional outcome between patients undergoing laparoscopic versus open resection for rectal adenocarcinoma. DESIGN: Cross-sectional prevalence of low anterior resection syndrome was assessed in a secondary analysis of the multicenter phase 3 randomized clinical trial, Australasian Laparoscopic Cancer of the Rectum Trial (ACTRN12609000663257). SETTING: There were 7 study subsites across New Zealand and Australia. PATIENTS: Participants were adults with rectal cancer who underwent anterior resection and had bowel continuity. MAIN OUTCOME MEASURES: Postoperative bowel function was evaluated using the validated low anterior resection syndrome score and Bowel Function Instrument. RESULTS: The Australasian Laparoscopic Cancer of the Rectum Trial randomized 475 patients with T1-T3 rectal adenocarcinoma less than 15 cm from the anal verge. A total of 257 participants were eligible for, and invited to, participate in additional follow-up; 163 (63%) completed functional follow-up. Overall cross-sectional prevalence of major low anterior resection syndrome was 49% (minor low anterior resection syndrome 27%). There were no differences in median overall Bowel Function Instrument score nor low anterior resection syndrome score between participants undergoing laparoscopic versus open surgery (66 vs 67, p = 0.52; 31 vs 27, p = 0.24) at a median follow-up of 69 months. LIMITATIONS: The major limitations are a result of conducting a secondary analysis; the likelihood of an insufficient sample size to detect a difference in prevalence between the groups and the possibility of selection bias as a subset of the randomized population was analyzed. CONCLUSIONS: Bowel dysfunction affects a majority of rectal cancer patients for a significant time after the operation. In this secondary analysis of a randomized trial, surgical approach does not appear to influence the likelihood or severity of low anterior resection syndrome. See Video Abstract at http://links.lww.com/DCR/B794. RESULTADO FUNCIONAL DE LA RESECCIN ASISTIDA POR LAPAROSCOPIA VERSUS RESECCIN ABIERTA EN CNCER DE RECTO ANLISIS SECUNDARIO DEL ESTUDIO DE CNCER DE RECTO LAPAROSCPICO DE AUSTRALASIA: ANTECEDENTES:El síndrome de resección anterior baja tiene un impacto significativo en la calidad de vida de los supervivientes de cáncer de recto. Los estudios anteriores que compararon la resección rectal laparoscópica con la abierta no han presentado resultados de la función intestinal.OBJETIVO:Evaluar si existe una diferencia en el resultado funcional entre los pacientes sometidos a resección laparoscópica versus resección abierta por adenocarcinoma de recto.DISEÑO:La prevalencia transversal del síndrome de resección anterior baja se evaluó en un análisis secundario del ensayo clínico aleatorizado multicéntrico de fase 3, Estudio Sobre el Cáncer de Recto Laparoscópico de Australasia (Australasian Laparoscopic Cancer of the Rectum Trial, ACTRN12609000663257).AJUSTE:Siete subsitios de estudio en Nueva Zelanda y Australia.PACIENTES:Los participantes eran adultos con cáncer de recto que se sometieron a resección anterior con anastomosis.PRINCIPALES MEDIDAS DE RESULTADO:La función intestinal posoperatoria se evaluó utilizando el previamente validado puntaje LARS y el Instrumento de Función Intestinal.RESULTADOS:El Estudio Sobre el Cáncer de Recto Laparoscópico de Australasia asignó al azar a 475 pacientes con adenocarcinoma rectal T1-T3 a menos de 15 cm del borde anal. 257 participantes fueron elegibles e invitados a participar en un seguimiento adicional. 163 (63%) completaron el seguimiento funcional. La prevalencia transversal general de LARS mayor fue del 49% (LARS menor 27%). No hubo diferencias en la puntuación media general del Instrumento de Función Intestinal ni en la puntuación LARS entre los participantes sometidos a cirugía laparoscópica versus cirugía abierta (66 frente a 67, p = 0,52; 31 frente a 27, p = 0,24) en una mediana de seguimiento de 69 meses.LIMITACIONES:Las principales limitaciones son el resultado de realizar un análisis secundario; se analizó la probabilidad de un tamaño de muestra insuficiente para detectar una diferencia en la prevalencia entre los grupos y la posibilidad de sesgo de selección como un subconjunto de la población aleatorizada.CONCLUSIONES:La disfunción intestinal afecta a la mayoría de los pacientes con cáncer de recto durante un tiempo significativo después de la operación. En este análisis secundario de un ensayo aleatorizado, el abordaje quirúrgico no parece influir en la probabilidad o gravedad del síndrome de resección anterior baja. Consulte Video Resumen en http://links.lww.com/DCR/B794. (Traducción-Dr. Felipe Bellolio).

Faecal incontinence is associated with an impaired rectosigmoid brake and improved by sacral neuromodulation.

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.

Meta-Analysis of the Composition of Human Intestinal Gases.

BACKGROUND: Understanding intestinal gases volume and composition may contribute to diagnosing digestive diseases and the microbiome's status. This meta-analysis aimed to define the composition of human intestinal gases and changes associated with diet. METHODS: Studies were identified by systematic research of the MEDLINE(Ovid), Scopus, and Cochrane databases. Studies that measured the concentration of intestinal gases in healthy adult humans were retrieved. The JBI critical appraisal tool was used to evaluate the risk of bias. The primary outcomes analysed were the concentration of the most prevalent colonic gases. Participants were divided into groups according to dietary fibre content. RESULTS: Eleven studies were included. The following gases were identified in similar concentrations across all studies (mean ± standard deviation): nitrogen (65.1 ± 20.89%), oxygen (2.3 ± 0.98%), carbon dioxide (9.9 ± 1.6%), hydrogen (2.9 ± 0.7%), and methane (14.4 ± 3.7%). Differences according to the dietary fibre were observed, with a positive correlation between fibre and volume of gas produced, particularly in fermented gases (carbon dioxide, hydrogen, and methane). DISCUSSION: The meta-analysis has found defined concentrations of the five most common gases present in human colonic gas. Limitations included heterogenic methodologies, a low number of participants, and few recent studies. These findings may be helpful in diagnostic applications where colonic gas volume and composition are crucial factors, including functional disorders, microbiome analyses, and bowel perforation diagnostics.

Intraoperative serosal extracellular mapping of the human distal colon: a feasibility study.

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.

Chyme reinfusion nutritional management for enterocutaneous fistula: first international application of a novel pump technique.

AIM: High-output enterocutaneous fistulas (ECFs) are an established cause of intestinal failure. Parenteral nutrition (PN) remains the gold standard for nutritional management but is complex, expensive and associated with significant complications. Chyme reinfusion (CR) has been reported by multiple centres as a viable option for nutritional management that improves nutritional status, provides the capacity to cease PN and is cost-effective. The aim of this paper is to describe the first use of a novel pump device (The Insides System™) by an independent centre in Australia for the nutritional management of a patient with high-output ECF. METHOD: CR was performed on a 66-year-old woman with a high-output ECF. The device consists of two main components: a centrifugal pump that sits inside the stoma appliance and a battery-powered driver that is magnetically coupled externally onto the pump. The device allows for bolus CR at a rate of infusion that is manually controlled by the patient based on comfort, volume and effluent viscosity. RESULTS: CR provided adequate nutritional support, with successful cessation of PN. Effective use of the device was learnt easily by the patient with minimal demands on nursing assistance. Side effects of CR (diarrhoea, abdominal cramping) were overcome by the patient's ability to manually adjust the reinfusion rate. CONCLUSION: Our experience with the novel Insides System™ device showed promising results in maintaining nutritional status as well as providing a minimally invasive, easy to use and low-cost system for CR. CR should be considered as a viable alternative for the nutritional management of patients with a high-output ECF.

Prolonged postoperative ileus following right- versus left-sided colectomy: A systematic review and meta-analysis.

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.

Altered colonic motility is associated with low anterior resection syndrome.

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.

Systematic review of peri-operative prognostic biomarkers in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential prognostic biomarkers to facilitate validation studies and clinical application. METHODS: A systematic review was performed (2004-2014) according to PRISMA guidelines. Studies were ranked using REMARK criteria and the following outcomes were examined: overall/disease free survival, nodal involvement, tumour characteristics, metastasis, recurrence and resectability. RESULTS: 256 biomarkers were identified in 158 studies. 171 biomarkers were assessed with respect to overall survival: urokinase-type plasminogen activator receptor, atypical protein kinase C and HSP27 ranked the highest. 33 biomarkers were assessed for disease free survival: CD24 and S100A4 were the highest ranking. 17 biomarkers were identified for lymph node involvement: Smad4/Dpc4 and FOXC1 ranked highest. 13 biomarkers were examined for tumour grade: mesothelin and EGFR were the highest ranking biomarkers. 10 biomarkers were identified for metastasis: p16 and sCD40L were the highest ranking. 4 biomarkers were assessed resectability: sCD40L, s100a2, Ca 19-9, CEA. CONCLUSION: This review has identified and ranked specific biomarkers that should be a primary focus of ongoing validation and clinical translational work in PDAC.

Postoperative ileus: mechanisms and future directions for research.

Postoperative ileus (POI) is an abnormal pattern of gastrointestinal motility characterized by nausea, vomiting, abdominal distension and/or delayed passage of flatus or stool, which may occur following surgery. Postoperative ileus slows recovery, increases the risk of developing postoperative complications and confers a significant financial load on healthcare institutions. The aim of the present review is to provide a succinct overview of the clinical features and pathophysiological mechanisms of POI, with final comment on selected directions for future research.Terminology used when describing POI is inconsistent, with little differentiation made between the obligatory period of gut dysfunction seen after surgery ('normal POI') and the more clinically and pathologically significant entity of a 'prolonged POI'. Both normal and prolonged POI represent a fundamentally similar pathophysiological phenomenon. The aetiology of POI is postulated to be multifactorial, with principal mediators being inflammatory cell activation, autonomic dysfunction (both primarily and as part of the surgical stress response), agonism at gut opioid receptors, modulation of gastrointestinal hormone activity and electrolyte derangements. A final common pathway for these effectors is impaired contractility and motility and gut wall oedema. There are many potential directions for future research. In particular, there remains scope to accurately characterize the gastrointestinal dysfunction that underscores an ileus, development of an accurate risk stratification tool will facilitate early implementation of preventive measures and clinical appraisal of novel therapeutic strategies that target individual pathways in the pathogenesis of ileus warrant further investigation.