Transcutaneous vagal nerve stimulation for treating gastrointestinal symptoms in individuals with diabetes: a randomised, double-blind, sham-controlled, multicentre trial.

AIMS/HYPOTHESIS: Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study. METHODS: This study included adults (aged 20-86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function. RESULTS: Sixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: -0.26 ± 0.64 vs -0.17 ± 0.62, p=0.44; GSRS: -0.35 ± 0.62 vs -0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: -0.47 ± 0.78 vs -0.33 ± 0.75, p=0.34; GSRS: -0.46 ± 0.90 vs -0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs -19 min, p=0.04). Segmental intestinal transit times and cardiovascular autonomic measurements did not differ between treatment groups (all p>0.05). The tVNS was well-tolerated. CONCLUSIONS/INTERPRETATION: Cervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04143269 FUNDING: The study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045).

EndoFLIP evaluation of the pylorus during minimal invasive Ivor-Levis esophagectomy.

BACKGROUND/AIMS: During esophagectomy for malignancy, the anterior and posterior branches of the vagus nerve are transected in order to achieve surgical radicality. This leads to loss of central nervous system-control of the pylorus which may lead to delayed gastric emptying. We aimed to investigate the feasibility of the EndoFLIP technique for assessment of pyloric biomechanical properties in patients undergoing esophagectomy. METHODS: A feasibility study in six patients undergoing surgery was conducted. EndoFLIP measurements were carried out preoperative (Pre-op), after surgical resection (Post-op) and following prophylactic balloon dilatation of the pylorus (Post-dil). By measuring the cross-sectional area and pressure of the pylorus the pyloric compliance and the incremental pressure-strain elastic modulus (Ep) were calculated. RESULTS: Placing the catheter in the pyloric region was successfully achieved in all six patients. No complications were observed. Resection of the esophagus increased the incremental pyloric elastic modulus (Ep) from 0.59 ± 0.18 kPa to 0.99 ± 0.34 kPa (p = 0.03). After dilatation, the Ep was reduced to 0.53 ± 0.23 kPa (p = 0.04), which was close to Pre-op (p = 0.62). The pyloric compliance showed a similar pattern as that found for Ep. CONCLUSION: The EndoFLIP system holds promise for assessment of biomechanics of the pyloric region in patients undergoing esophagectomy for cancer.

Opium tincture has anti-propulsive effects in patients with chronic diarrhea: a randomized, placebo-controlled, and cross-over trial.

OBJECTIVE: Chronic diarrhea affects approximately 5% of the population. Opioids inhibit gastrointestinal motility, and opium tincture has shown anti-propulsive effects in healthy, but no controlled studies of its clinical efficacy exist. We aimed to investigate the anti-propulsive and central nervous system (CNS) effects of opium tincture in patients with chronic diarrhea. MATERIALS AND METHODS: The study was a randomized, double-blinded, placebo-controlled, cross-over trial in subjects with chronic diarrhea refractory to standard treatment. Participants received opium tincture or placebo during two intervention periods, each lasting seven days. Bowel movements were recorded daily, and gastrointestinal transit time was investigated with the wireless motility capsule system. Gastrointestinal symptoms, health-related quality of life, and CNS effects (pupil size, reaction time, memory, and general cognition) were also investigated, along with signs of addiction. RESULTS: Eleven subjects (mean age: 45 ± 17 years, 46% males) with a median of 4.7 daily bowel movements were included. The number of daily bowel movements was reduced during opium tincture treatment to 2.3 (p = 0.045), but not placebo (3.0, p = 0.09). Opium tincture prolonged the colonic transit time compared to placebo (17 h vs. 12 h, p < 0.001). In both treatment arms, there were no changes in self-reported gastrointestinal symptoms, health-related quality of life, or CNS effects, and no indication of addiction was present. CONCLUSION: Opium tincture induced anti-propulsive effects in patients with chronic diarrhea refractory to standard treatment. This indicates that opium tincture is a relevant treatment strategy for selected patients with chronic diarrhea. Moreover, no evidence of opioid-induced sedation or addiction was found.Trial Registration Number: NCT05690321 (registered 2023-01-10).

Efficacy of Injection of Freshly Collected Autologous Adipose Tissue Into Complex Cryptoglandular Anal Fistulas.

BACKGROUND: Treatment of cryptoglandular anal fistulas with injection of autologous or allogenic adipose tissue-derived mesenchymal stem cells has shown promising results. However, allogenic adipose tissue-derived mesenchymal stem cells are expensive and use of autologous adipose tissue-derived mesenchymal stem cells requires preceding liposuction and isolation of stem cells, time for cell culture, and laboratory facilities. Freshly collected autologous adipose tissue may be an easily available and inexpensive alternative. OBJECTIVE: This study aimed to investigate the efficacy of injection with freshly collected autologous adipose tissue into complex cryptoglandular anal fistulas. DESIGN: Prospective cohort study. SETTING: Single tertiary center for treatment of cryptoglandular fistulas in Denmark. PATIENTS: This study included 77 patients with complex cryptoglandular anal fistulas. INTERVENTIONS: The intervention included injections of freshly collected autologous adipose tissue. Patients not achieving healing after 8 to 12 weeks were offered a second injection. MAIN OUTCOME MEASURES: Primary outcome was fistula healing defined as no symptoms of discharge and no visible external and palpable internal opening by anorectal digital examination at clinical evaluation 6 months after final treatment. Secondary end points were combined clinical and MRI fistula healing, reduced fistula secretion and anal discomfort, and complications to the treatment. RESULTS: Thirty-nine patients (51%) achieved the primary outcome of fistula healing 6 months after their final treatment. Nine patients (12%) experienced reduced secretion and decreased anal discomfort. Thirty-seven patients (48%) achieved combined clinical and MRI fistula healing. Treatment was well tolerated; 5 patients (4%) experienced serious adverse events (infection or bleeding) requiring surgical intervention. LIMITATIONS: No control group was included. CONCLUSION: Injection of freshly collected autologous adipose tissue is a safe treatment of complex cryptoglandular anal fistulas and may be an easily accessible inexpensive alternative to cultured autologous and allogenic adipose tissue-derived mesenchymal stem cells. See Video Abstract at http://links.lww.com/DCR/C45 . EFICACIA DE LA INYECCIN DE TEJIDO ADIPOSO AUTLOGO RECIN RECOLECTADO EN FSTULAS ANALES CRIPTOGLANDULARES COMPLEJAS: ANTECEDENTES:El tratamiento de las fístulas anales criptoglandulares con inyección de células madre mesenquimales derivadas de tejido adiposo autólogo o alogénico ha mostrado resultados prometedores. Sin embargo, las células madre mesenquimales derivadas de tejido adiposo alogénicas son costosas y el uso de células madre mesenquimales derivadas de tejido adiposo autólogas requiere una liposucción previa y el aislamiento de las células madre, tiempo para el cultivo celular e instalaciones de laboratorio. El tejido adiposo autólogo recién recolectado puede ser una alternativa económica y de fácil acceso.OBJETIVO:Investigar la eficacia de la inyección con tejido adiposo autólogo recién recolectado en fístulas anales criptoglandulares complejas.DISEÑO:Estudio de cohorte prospectivo.ESCENARIO:Centro terciario para el tratamiento de fístulas criptoglandulares en Dinamarca.PACIENTES:Setenta y siete pacientes con fístulas anales criptoglandulares complejas.INTERVENCIONES:Inyecciones de tejido adiposo autólogo recién recolectado. A los pacientes que no lograron la curación después de 8 a 12 semanas se les ofreció una segunda inyección.MEDIDAS DE RESULTADO PRINCIPALES:El resultado primario fue la cicatrización de la fístula definida como ausencia de síntomas de secreción, apertura externa visible e interna palpable mediante examen digital anorrectal en la evaluación clínica 6 meses después del tratamiento final. Los resultados secundarios fueron la combinación clínica y de curación en la resonancia magnética, la reducción de la secreción de la fístula y las molestias anales, y las complicaciones del tratamiento.RESULTADOS:Treinta y nueve pacientes (51%) lograron el resultado primario de curación de la fístula 6 meses después de su tratamiento final. Nueve pacientes (12%) experimentaron una reducción de la secreción y una disminución de las molestias anales. Treinta y siete pacientes (48%) lograron la curación combinada de la fístula clínica y en la resonancia magnética. El tratamiento fue bien tolerado; 5 pacientes (4%) experimentaron eventos adversos graves (infección o sangrado) que requirieron intervención quirúrgica.LIMITACIONES:No se incluyó ningún grupo de control.CONCLUSIÓN:La inyección de tejido adiposo autólogo recién recolectado es un tratamiento seguro de las fístulas anales criptoglandulares complejas y puede ser una alternativa económica de fácil acceso a las células madre mesenquimales derivadas de tejido adiposo autólogo y alogénico cultivadas. Consulte Video Resumen en http://links.lww.com/DCR/Cxx . (Traducción-Dr. Felipe Bellolio ).

Pan-alimentary assessment of motility, luminal content, and structures: an MRI-based framework.

BACKGROUND: Gastrointestinal symptoms originating from different segments overlap and complicate diagnosis and treatment. In this study, we aimed to develop and test a pan-alimentary framework for the evaluation of gastrointestinal (GI) motility and different static endpoints based on magnetic resonance imaging (MRI) without contrast agents or bowel preparation. METHODS: Twenty healthy volunteers (55.6 ± 10.9 years, BMI 30.8 ± 9.2 kg/m2) underwent baseline and post-meal MRI scans at multiple time points. From the scans, the following were obtained: Gastric segmental volumes and motility, emptying half time (T50), small bowel volume and motility, colonic segmental volumes, and fecal water content. Questionnaires to assess GI symptoms were collected between and after MRI scans. KEY RESULTS: We observed an increase in stomach and small bowel volume immediately after meal intake from baseline values (p<.001 for the stomach and p=.05 for the small bowel). The volume increase of the stomach primarily involved the fundus (p<.001) in the earliest phase of digestion with a T50 of 92.1 ± 35.3 min. The intake of the meal immediately elicited a motility increase in the small bowel (p<.001). No differences in colonic fecal water content between baseline and 105 min were observed. CONCLUSION & INFERENCES: We developed a framework for a pan-alimentary assessment of GI endpoints and observed how different dynamic and static physiological endpoints responded to meal intake. All endpoints aligned with the current literature for individual gut segments, showing that a comprehensive model may unravel complex and incoherent gastrointestinal symptoms in patients.

Bowel dysfunction following pelvic organ cancer: a prospective study on the treatment effect in nurse-led late sequelae clinics.

BACKGROUND: Bowel dysfunction following treatment of pelvic organ cancer is prevalent and impacts the quality of life (QoL). The present study aimed to evaluate the feasibility and effects of treating bowel dysfunction in two nurse-led late sequelae clinics. MATERIAL AND METHODS: Treatment effects were monitored prospectively by patient-reported outcome measures collected at baseline and discharge. Change in bowel function was evaluated by 15 bowel symptoms, the St. Mark's Incontinence Score, the Patients Assessment of Constipation-Symptoms (PAC-SYM) score and self-rated bowel function. QoL was evaluated by the EuroQol 5-dimension 5-level (EQ-5D-5L) utility score and by measuring the impact of bowel function on QoL. RESULTS: From June 2018 to December 2021, 380 cancer survivors (46% rectal, 15% gynaecological, 13% anal, 12% colon, 12% prostate, and 2% other cancers) completed a baseline questionnaire and started treatment for bowel dysfunction. At referral, 96% of patients were multisymptomatic. The most frequent symptoms were faecal urgency (95%), fragmented defaecation (93%), emptying difficulties (92%), flatus/faecal incontinence (flatus 89%, liquid 59%, solid 33%), and obstructed defaecation (79%). In total, 169 patients were discharged from the clinics in the follow-up period. At discharge, 69% received conservative treatment only and 24% also received transanal irrigation; 4% were surgically treated; 3% discontinued treatment. Improvements were seen in all 15 bowel symptoms (p < 0.001), the mean St. Mark's Incontinence Score (12.0 to 9.9, p < 0.001), the mean PAC-SYM score (1.04 to 0.84, p < 0.001) and the mean EQ-5D-5L utility score (0.78 to 0.84, p < 0.001). Self-rated bowel function improved in 56% (p < 0.001) of cases and the impact of bowel function on QoL improved in 46% (p < 0.001). CONCLUSION: Treatment of bowel dysfunction in nurse-led late sequelae clinics is feasible and significantly improved bowel function and QoL.

Prospective evaluation of bowel function and quality of life after colon cancer surgery - is it time for routine screening for late sequelae?

AIM: Bowel dysfunction after colon cancer (CC) surgery is widely neglected in current follow up programmes. This study explored changes in bowel function and quality of life (QoL) from three (3 m) to twelve months (12 m) after surgery in CC patients undergoing right- or left-sided colon resection (RightSCR/LeftSCR) and investigated differences between the two groups 12 m after surgery. METHOD: CC patients undergoing surgical resection in 2018-2020 at five surgical departments were included in this population-based prospective cohort study. Included patients completed electronic surveys consisting of a collection of validated scores 3 m and 12 m after surgery. RESULTS: A total of 708 CC patients (423 RightSCR, 285 LeftSCR) were included. In RightSCR, no improvement was observed from 3 m to 12 m in most scores/items, on the contrary, symptom worsening in flatus- and faecal incontinence and urgency was observed (p < 0.05). Also, the proportion of patients rating their bowel function as very good/good decreased (p < 0.05) in this group. In LeftSCR improvement was found in flatus and faecal incontinence, urgency and night-time defaecation (p < 0.02), while no improvement was observed in the remaining scores/items. At 12 m, higher proportions of RightSCR than LeftSCR reported loose stools, incontinence and urgency (all p < 0.001), whereas LeftSCR more often reported hard stools and flatus incontinence (p < 0.05). Among all CC patients 18.3% reported bowel-related impairment of QoL at 12 m with no differences between the two groups. CONCLUSION: From 3 m to 12 m no significant change was observed in the majority of bowel function and QoL scores/items, however, some symptoms worsened in RightSCR, while a few improved in LeftSCR. Bowel dysfunction and impaired QoL were still common in both groups at 12 m, although the symptom pattern differed between the groups. These findings call for a systematic screening for bowel dysfunction to ensure early treatment of symptoms.

Chronic loose stools following right-sided hemicolectomy for colon cancer and the association with bile acid malabsorption and small intestinal bacterial overgrowth.

AIM: Patients treated with right-sided hemicolectomy for colon cancer may suffer from long-term bowel dysfunction, including loose stools, urgency and faecal incontinence. The underlying causes are poorly understood. The aim of this case-control study was to investigate the aetiology of chronic loose stools among patients with right-sided hemicolectomy curatively operated for cancer. METHOD: Cases with chronic loose stools (Bristol stool type 6-7) after right-sided hemicolectomy were compared with a control group of patients with right-sided hemicolectomy without loose stools. All patients underwent a selenium-75 homocholic acid taurine (SeHCAT) scan to diagnose bile acid malabsorption (BAM) and a glucose breath test to diagnose small intestinal bacterial overgrowth (SIBO). Gastrointestinal transit time (GITT) was assessed with radiopaque markers. In a subgroup of patients, fibroblast growth factor 19 (FGF19) was measured in fasting blood. SIBO was treated with antibiotics and BAM was treated with bile acid sequestrants. RESULTS: We included 45 cases and 19 controls. In the case group, 82% (n = 36) had BAM compared with 37% (n = 7) in the control group, p < 0.001. SIBO was diagnosed in 73% (n = 33) of cases with chronic loose stools and in 74% (n = 14) of controls, p = 0.977. No association between BAM and SIBO was observed. GITT was similar in cases and controls. No difference in median FGF19 was observed between cases and controls (p = 0.894), and no correlation was seen between FGF19 and SeHCAT retention (rs 0.20, p = 0.294). Bowel symptoms among cases were reduced after treatment. CONCLUSION: BAM and SIBO are common in patients having undergone right-sided hemicolectomy for cancer. Chronic loose stools were associated with BAM but not with SIBO.

Are local analgesics effective in reducing autonomic dysreflexia in individuals with spinal cord injury? A systematic review.

STUDY DESIGN: Systematic review. OBJECTIVES: To systematically review the evidence on the use of local analgesics, specifically lidocaine or bupivacaine, to prevent autonomic dysreflexia (AD) during iatrogenic procedures or bowel and bladder care routines in individuals with spinal cord injury (SCI). METHODS: A keyword search of MEDLINE, CINAHL, CENTRAL, Cochrane Reviews, PsycInfo, Embase, and Web of Science databases identified all English-language studies evaluating the efficacy of local analgesics in reducing AD. Included studies were either randomized controlled trials (RCTs) or quasi-experimental studies. Participants were adults with chronic SCI who received local analgesics prior to AD-triggering procedures or routines. Additionally, studies were required to report blood pressure values as an outcome. The methodology of this review followed the PRISMA checklist and was registered with PROSPERO (CRD42021219506). RESULTS: Four RCTs and two quasi-experimental studies met inclusion criteria. Results were narratively synthesized as meta-analysis was not possible due to heterogeneity across studies included in the review. All six studies administered lidocaine. Lidocaine was found to have a beneficial effect on AD in three studies, no effect in two studies and a detrimental effect in one study. CONCLUSIONS: Presently, RCTs and quasi-experimental studies on the use of lidocaine for reducing AD in individuals with SCI had small sample sizes and opposing findings. There is a strong need for definitive, well-monitored clinical trials with adequate sample sizes. Presently there is not enough compelling evidence to support or refute recommendations for the use of lidocaine from the AD management clinical practice guidelines.

Diet and bowel symptoms among colon cancer survivors.

BACKGROUND: Survival from colon cancer (CC) has improved considerably over the last decades, yet many survivors suffer from late sequelae from treatment. Typical symptoms of bowel dysfunction after treatment of CC are diarrhea, urge for defecation, fecal incontinence, bloating and constipation. Most CC survivors make dietary changes to alleviate bowel symptoms. We aimed to describe the self-perceived effects of diet on bowel function among CC survivors and the level of dietary information given. MATERIALS AND METHODS: In this cross-sectional study, CC patients from four surgical departments in Denmark completed surveys regarding the effects of diet on their bowel function and whether they had previously received dietary advice. Data concerning sociodemographic characteristics and the surgical procedure (right-sided or left-sided hemicolectomy) were collected from the Danish Colorectal Cancer Group database. Forty-four healthcare professionals specialized in CC completed a questionnaire on how they advise CC. Descriptive statistics were applied. RESULTS: Among 1544 patients invited, 1239 (80.4%) responded, and 844 met the inclusion criteria (53% males, median age 72.6 years, median time since surgery 742 days). Among these, 267 (32%) reported that food affected bowel function. Fat was perceived to have a negative effect in 193 (25%), spices in 149 (19%), sweets in 101 (13%) and meat in 99 (13%). There was no association between tumor site and food categories affecting bowel function (p = 0.078). Most healthcare professionals (93%) stated that their unit gave advice about diet, but only 24% of patients remembered such information. CONCLUSION: One-third of CC survivors perceive that food items, especially fat and spices have a negative impact on their bowel function. We found a major discrepancy between healthcare professionals reporting that they provide advice and the proportion of patients remembering this. There is an unmet need for further recognition of the role of diet in CC rehabilitation and for intervention studies of treatment principles.

Hypertriglyceridemia is often under recognized as an aetiologic risk factor for acute pancreatitis: A population-based cohort study.

BACKGROUND: Severe hypertriglyceridemia (HTG) is a well-known risk factor for acute pancreatitis, but updated population-based estimates on incidence of HTG-associated pancreatitis are lacking. METHODS: We identified all individuals with severe HTG (triglyceride level >10 mmol/L [886 mg/dL]) in a population-based sample from 2008 to 2019 and linked these with Danish nationwide health-registers to identify patients with acute pancreatitis. Pancreatitis cases were subsequently confirmed by a detailed medical chart review. Crude and standardized incidence rates were estimated and studied in relation to age, gender and time-period. In addition, aetiological classification designated during index hospitalization, severity and follow-up of individuals with HTG-associated pancreatitis were studied. RESULTS: Among 2146 individuals with severe HTG during the observation period, 75 were diagnosed with acute pancreatitis (3.5%). The mean incidence rate of HTG-associated pancreatitis was 1.4 (95% CI, 1.1-1.7) per 100,000 person years for the total population, for women it was 0.7 (95% CI, 0.5-1.1) and for men 2.0 (95% CI, 1.5-2.6) per 100,000 person-years. The mean incidence rate increased from 0.7 to 1.7 per 100,000 person-years from 2008 to 2019 (ptrend = 0.01). The highest incidence rate of HTG-associated pancreatitis was observed for men in the age group 50-59 years. An elevated triglyceride level was recognized as aetiological risk factor in 35% of patients during index hospitalization. CONCLUSIONS: Only a fraction of patients with severe HTG are hospitalized for acute pancreatitis, but the incidence is increasing. In more than half of patients elevated triglycerides is not recognized as a risk factor for acute pancreatitis during index hospitalization.

Effectiveness of infliximab treatment of complex idiopathic anal fistulas.

OBJECTIVES: To investigate the effects of infliximab treatment in patients with complex idiopathic anal fistulas refractory to standard surgical treatment. MATERIALS AND METHODS: We retrospectively evaluated the effects ofinfliximab treatmentin patients with complex idiopathic anal fistulas refractory to standard surgical intervention. The primary outcome was achievement of substantial clinical improvement defined as sustained, reduced inflammatory activity at perioperativeevaluation, i.e., only minimal-to-moderate secretion and induration and a reduction of fistula size of a magnitude that would make it possible to perform a lay-open or sphincter-sparring closure procedure. Secondary outcomes weresymptom improvement, adverse treatment events and fistula healing after the surgical procedure in those achieving the primary outcome. RESULTS: Twenty-two patients were included (18 high transsphincteric, 3complex low transsphincteric, 1 suprasphincteric fistula). Fistulas had been present for a median of 24 [interquartile range, IQR: 12-33] months. In total, 16 patients (73%) achieved the primary outcome of substantial clinical improvement. Median time from infliximab initiation to patients achieved the primary outcome was 11 [IQR: 8-22] months. Sixteen of the patients responding to infliximab received subsequent lay-open or sphincter-sparring closure procedure surgery. Of these, ten (63%) achieved fistula healing. No serious infectious complications to infliximab treatment were seen. One patient developed a new abscess. One patient developed psoriasis (pustolosispalmoplantaris). CONCLUSIONS: Infliximab treatment may be considered a supplement to repeated curettage and setondrainage in the management of selected, complex idiopathic anal fistulas. Such combined treatment may make otherwise refractory fistulas amenable to definitive closure attempts.

Regional Gastrointestinal Motility in Healthy Children.

OBJECTIVE: The aim of the study was to evaluate the safety and use of the 3D-Transit system (Motilis SA, Lausanne, Switzerland) and to describe regional gastrointestinal transit times, segmental colonic transit times, and colonic movement patterns in healthy children. METHODS: Twenty-one healthy children (11 girls, median age 10.5 years, range 7-15 years) were included. For evaluation of gastrointestinal transit times and colonic movement patterns, we used the minimally invasive electromagnetic 3D-Transit system. A small electromagnetic capsule (21.5 mm × 8.3 mm) was ingested and tracked through the gastrointestinal tract by a body-worn detector. Regional gastrointestinal transit times were assessed as time between capsule passage of anatomical landmarks. Colonic movement patterns were described and classified based on capsule movement velocity, direction, and distance. RESULTS: One child could not swallow the capsule and 20 children completed the study without any discomfort or side-effects. Median whole gut transit time was 33.6 (range 10.7-80.5) hours, median gastric emptying time was 1.9 (range 0.1-22.1) hours, median small intestinal transit time was 4.9 (range 1.1-15.1) hours, and median colonic transit time was 26.4 (range 6.8-74.5) hours. Median ascending colon/cecum transit time was 9.7 (range 0.3-48.1) hours, median transverse colon transit time was 5.6 (range 0.0-11.6) hours, median descending colon transit time was 2.6 (range 0.01-22.3) hours, and median sigmoid colon/rectum transit time was 7.5 (range 0.1-31.6) hours. Colonic movement patterns among children corresponded to those previously described in healthy adults. CONCLUSIONS: The 3D-Transit system is a well-tolerated and minimally invasive method for assessment of gastrointestinal motility in children.

Systematic screening for late sequelae after colorectal cancer-a feasibility study.

AIM: The aim of this study was to test the feasibility of a new method for systematic screening for late sequelae (LS) following colorectal cancer treatment. METHOD: Patients with colorectal cancer from five Danish hospitals were invited to complete a survey about LS at 3, 12, 24 and 36 months after surgery as part of their follow-up. The survey consisted primarily of validated tools, supplemented by a few ad hoc items, measuring bowel, urinary and sexual dysfunction, pain and quality of life and an additional question regarding request for contact. Patients completed surveys electronically or on paper. RESULTS: Of the 1721 invited patients, 1386 (80.5%) were included (1085 with colon cancer and 301 with rectal cancer) of whom 72.5% responded electronically. Patients responding electronically were 7.6 years younger than those responding on paper (P < 0.001). Since some patients answered more than once, the dataset consisted of 2361 surveys. Patients with colon cancer requested phone contact in 19.0% of the surveys, and 8.4% were referred to treatment for LS, primarily bowel dysfunction. Among patients with rectal cancer, 30.8% requested phone contact and 16.2% were referred for treatment of LS, mainly due to bowel and sexual dysfunction. CONCLUSION: This is the first paper investigating a new method of systematic screening for LS following colorectal cancer using electronic patient-reported outcome measures. The study shows that in the Danish population a high response rate can be obtained with this method and that close to three-quarters of patients respond electronically. Patients with rectal cancer had a higher need for phone contact and treatment of LS than patients with colon cancer.

Long-term anorectal function in rectal cancer patients treated with chemoradiotherapy and endorectal brachytherapy.

AIM: The aim was to study anorectal function in long-term survivors after combined, curatively intended, chemoradiotherapy and endorectal brachytherapy for low rectal cancer. METHODS: This was a case-control design. We compared anorectal function by anal manometry, anal functional lumen imaging probe (EndoFLIP) and rectal bag distension in rectal cancer patients (RCPs) and healthy, normal subjects (NSs). Symptoms were assessed by the low anterior resection syndrome (LARS) and Wexner faecal incontinence scores. RESULTS: Thirteen RCPs (12 men, median age 68 years, range 52-92) after 60 Gy radiotherapy, 5 Gy endorectal brachytherapy and oral tegafur-uracil with complete clinical response (median time since treatment 2.8 years, range 2.2-5.6) were compared to 15 NSs (14 men, median age 64 years, range 47-75). RCPs had lower than normal anal resting pressure, 38.6 mmHg (range 8.8-67.7) versus 58.8 mmHg (25.7-105.2) (P < 0.003), and squeeze pressure, 117 mmHg (55.2-203) versus 188 mmHg (103-248) (P < 0.01). Squeeze-induced pressure increase recorded by EndoFLIP was also lower in RCPs (q > 7.56, P < 0.001) as was the anal canal resistance to increasing distension (q = 3.13, P < 0.05). No differences in median rectal volume at first sensation (72 [22-158] vs. 82 [36-190] ml, P = 0.4) or at urge to defaecate (107 [42-227] vs. 132 [59-334] ml, P = 0.2) were found. However, maximum tolerable rectal volume was lower in RCPs (145 [59-319] vs. 222 [106-447] ml, P < 0.02). The median (range) low anterior resection syndrome score was 27 (0-39) for RCPs and 7 (0-23) for NSs (P < 0.001), while the Wexner score was 0 (0-5) versus 0 (0-4) (P = 0.56). CONCLUSION: Radiotherapy combined with endorectal brachytherapy for rectal cancer causes long-term anorectal symptoms, impaired anal sphincter function and reduced rectal capacity.

Long-term gastrointestinal sequelae in colon cancer survivors: prospective pilot study on identification, the need for clinical evaluation and effects of treatment.

AIM: The aim of the present pilot study was to describe the type and frequency of long-term gastrointestinal symptoms within a well-defined cohort of colon cancer survivors, their wish for clinical evaluation and treatment outcomes. METHOD: A screening survey was sent to colon cancer survivors 12, 24 and 36 months after surgery. Based on their main symptoms, patients who wished to have a consultation were referred to the gastroenterological or surgical unit of our late cancer sequelae clinic. Treatment effect was monitored by questionnaires on bowel symptoms and the EuroQol five-dimensional (EQ-5D) quality-of-life score. RESULTS: Overall, 953 patients who had survived colon cancer received the screening survey and 767 replied (response rate 80.5%). Of these, 76 (9.9%; 95% CI 7.9%-12.2%) were referred for algorithm-based clinical evaluation and treatment of bowel dysfunction. The majority were women (69.7%) who had undergone a right-sided colonic resection (65.8%). Patients reported various symptoms, mainly including urgency, fragmented defaecation, loose stools and incontinence for liquid stools. Patients with emptying difficulties and low anterior resection syndrome-like symptoms were referred to the surgical unit and patients with diarrhoea were referred to the gastroenterological unit for clinical work-up. Our main endpoint, mean EQ-5D index after treatment, was improved compared with baseline (baseline 0.809, after treatment 0.846; p = 0.049). After treatment, self-rated bowel function and several bowel symptoms were improved as well. CONCLUSION: This study highlights the importance of identifying colon cancer survivors in need of treatment of late gastrointestinal sequelae and clinical management in a multidisciplinary team setting.

Colorectal dimensions in the general population: impact of age and gender.

PURPOSE: Constipation is among the most common gastrointestinal disorders, although, there is no generally accepted objective diagnostic criteria thereof. It has been proposed that colorectal dimensions assessed with Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) may support the diagnosis, but normative data are lacking. The aim of this study was to describe colorectal dimensions in a sample of the general population and to investigate whether the dimensions were under influence by age and gender. METHODS: The maximum diameters and cross-sectional areas of the ascending colon, descending colon and rectum were determined from 119 CT scans of trauma patients (age groups from 15 to 70 years, 84 men and 35 women). A regression model was applied to explore the impact of age and gender on colorectal dimensions. RESULTS: Overall, great variations were found for all colorectal diameters and cross-sectional areas (median diameter (5% percentiles; 95% percentiles): ascending 46 (26; 63) mm; descending 29 (16; 48) mm; rectum 39 (22; 67) mm. Women had larger rectal cross-sectional areas, reflecting more rectal content, compared to men (p = 0.003). Age did not affect colorectal diameters or cross-sectional areas (all p > 0.10). CONCLUSION: Great variations of colorectal dimensions were found. Larger rectal cross-sectional areas in women could likely reflect the fact that women have increased prevalence of constipation. Future studies should take gender into consideration when evaluating colorectal dimensions.

Efficacy of Injection of Freshly Collected Autologous Adipose Tissue Into Perianal Fistulas in Patients With Crohn's Disease.

BACKGROUND & AIMS: Perianal fistulas are common in patients with Crohn's disease (CD). Injections of cultured autologous and allogeneic adipose tissue-derived stem cells have been shown to heal CD-associated fistulas. Unfortunately, this treatment is time consuming and expensive. We investigated the effects of injecting freshly collected autologous adipose tissue into perianal fistulas in patients with CD. METHODS: In a prospective interventional study, freshly collected autologous adipose tissues were injected into complex perianal fistulas of 21 patients with CD, from March 2015 through June 2018. The primary endpoint was complete fistula healing (no symptoms of discharge, no visible external fistula opening in the perineum, and no internal opening detected by rectal digital examination) 6 months after the last injection. We performed pelvic magnetic resonance imaging to confirm fistula resolution in patients with intersphincter and transsphincter fistulas who showed complete healing at clinical examination. Patients without complete fistula healing after 6 weeks and those with later relapse were offered additional injections. No control individuals were included. RESULTS: Six months after the last adipose tissue injection, 12 patients (57%) had complete fistula healing. Three patients (14%) had ceased fistula secretion, and 1 patient (5%) reported reduced secretion. Among 10 patients with trans-sphincter or inter-sphincter fistulas, magnetic resonance imaging showed complete fistula resolution in 9 patients and a markedly reduced gracile fistula in the remaining patient. Of the 12 patients with complete fistula healing, 9 (43%) required 1 injection, 2 (10%) required 2 injections, and 1 (5%) required 3 injections. The predominant adverse effect was postprocedure proctalgia lasting a few days. Two patients developed small abscesses, 1 had urinary retention, and 1 had minor bleeding during liposuction. CONCLUSION: In a study of 21 patients with CD and perianal fistulas, we found injection of recently collected autologous adipose tissue to be safe and to result in complete fistula healing in 57% of patients. ClinicalTrials.gov, Number: NCT03803917.

Abnormal Neuronal Response to Rectal and Anal Stimuli in Patients Treated for Distal Rectal Cancer With High-Dose Chemoradiotherapy Followed By Watchful Waiting.

BACKGROUND: Watchful waiting in patients with rectal cancer with complete clinical response after chemoradiation therapy has gained increased popularity to avoid morbidity and mortality associated with surgery. Irradiation of the pelvis causes bowel dysfunction, but the effect on anorectal sensory function remains obscure in this patient category. OBJECTIVE: The aim of this study was to characterize the sensory pathways of the gut-brain axis in patients with rectal cancer treated solely with chemoradiation therapy (nonconventional regime/dose) compared with healthy volunteers. DESIGN: This is an explorative study. SETTINGS: Sensory evaluation by rectal distension was performed and cortical evoked potentials were recorded during rapid balloon distensions of the rectum and anal canal. Latencies and amplitudes of cortical evoked potentials were compared, and the relative amplitude of 5 spectral bands from recorded cortical evoked potentials was used as an additional proxy of neuronal processing. PATIENTS: Patients with rectal cancer solely with chemoradiation therapy (n = 13) a median of 3.2 years ago (range, 2.3-5.6 y) and healthy volunteers (n = 13) were included. MAIN OUTCOME MEASURES: Cortical evoked potentials were measured. RESULTS: Patients had 35% lower rectal capacity at a maximum tolerable volume (p = 0.007). We found no differences in rectal cortical evoked potential latencies (p = 0.09) and amplitudes (p = 0.38) between groups. However, spectral analysis of rectal cortical evoked potentials showed a decrease in θ (4-8 Hz) and an increase in ß (12-32 Hz) band activity in patients (all p < 0.001). Anal cortical potentials showed an increase in α (8-12 Hz) and ß and a decrease in γ (32-70 Hz) band activity (all p < 0.001) in patients compared with healthy volunteers. LIMITATIONS: This is an explorative study of limited size. CONCLUSIONS: Chemoradiation therapy for distal rectal cancer causes abnormal cortical processing of both anal and rectal sensory input. Such central changes may play a role in symptomatic patients, especially when refractory to local treatments. See Video Abstract at http://links.lww.com/DCR/B270. RESPUESTA NEURONAL ANORMAL A ESTÍMULOS RECTALES Y ANALES, EN PACIENTES TRATADOS POR CÁNCER RECTAL DISTAL, CON QUIMIORRADIOTERAPIA DE DOSIS ALTA, SEGUIDA DE ESPERA VIGILANTE: La espera vigilante en pacientes de cáncer rectal, con respuesta clínica completa después de la quimiorradiación, ha ganado una mayor popularidad en evitar la morbilidad y mortalidad asociadas con la cirugía. La irradiación de la pelvis causa disfunción intestinal, pero el efecto sobre la función sensorial ano-rectal sigue siendo no claro, en esta categoría de pacientes.El objetivo de este estudio, fue caracterizar las vías sensoriales del eje intestino-cerebro en pacientes con cáncer rectal, tratados únicamente con quimiorradiación (régimen / dosis no convencional), en comparación con voluntarios sanos.Es un estudio exploratorio.Se realizó una evaluación sensorial por distensión rectal y se registraron los potenciales evocados corticales, durante las distensiones rápidas con balón en recto y canal anal. Se compararon las latencias y amplitudes de los potenciales evocados corticales, y la amplitud relativa de cinco bandas espectrales registradas, de potenciales evocados corticales, se usaron como proxy adicional del procesamiento neuronal.Pacientes de cáncer rectal, únicamente con terapia de quimiorradiación (n = 13) mediana de 3.2 años (rango 2.3-5.6) y voluntarios sanos (n = 13).Potenciales evocados corticales.Pacientes tuvieron una capacidad rectal menor del 35%, al volumen máximo tolerable (p = 0.007). No encontramos diferencias en las latencias potenciales evocadas corticales rectales (p = 0.09) y amplitudes (p = 0.38) entre los grupos. Sin embargo, el análisis espectral de los potenciales evocados corticales rectales, mostró una disminución en theta (4-8 Hz) aumento en beta (12-32 Hz), y actividad en banda en pacientes (todos p <0.001). Los potenciales evocados corticales anales mostraron un aumento en alfa (8-12 Hz) y beta, disminución en gamma (32-70 Hz), y actividad en banda (todos p <0.001), en pacientes comparados a voluntarios sanos.Este es un estudio exploratorio de tamaño limitado.La quimiorradiación para el cáncer rectal distal, ocasiona procesos corticales sensoriales anormales anales y rectales. Tales cambios centrales pueden desempeñar un papel en pacientes sintomáticos, especialmente cuando son refractarios a tratamientos locales. Consulte Video Resumen en http://links.lww.com/DCR/B270.

Creation and validation of a new tool for the monitoring efficacy of neurogenic bowel dysfunction treatment on response: the MENTOR tool.

STUDY DESIGN: Prospective observational study. OBJECTIVES: A tool to help decision-making tool for Neurogenic Bowel Dysfunction (NBD) in individuals with SCI is needed. We present a project to create and validate a new tool, the Monitoring Efficacy of NBD Treatment On Response (MENTOR), and to determine its level of concordance with decisions made by experienced clinicians in the field. SETTING: UK, Denmark, USA, Italy, The Netherlands, Germany. METHODS: The first phase was creation of the tool through a modified Delphi process. The second phase was the validation, wherein individuals with spinal cord injury with NBD were asked to complete the MENTOR tool immediately prior to clinic consultation. From the responses to the questionnaire of the tool, each participant was allocated into one of three categories reflecting the possible therapeutic recommendations ("recommend change", "further discussion" and "monitoring"). An expert clinician then assessed the participant, blinded to MENTOR results, and made an independent treatment decision. RESULTS: A total of 248 MENTOR forms were completed. Strong agreement was found when the MENTOR tool recommended monitoring (92%) or treatment change (83%); the lowest concordance when the decision was for the "further discussion" option (59%). Patient acceptability was reported by 97% of individuals. CONCLUSIONS: MENTOR is an easy to use tool to monitor the treatment of NBD and determinate progression through the clinical pathway. This validation study shows good correspondence between expert clinician opinion and MENTOR result. The tool has potential to be used in other patient groups, following further studies.