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Background: Opioids inhibit motility and secretion of the gut and have been used for antidiarrheal treatment for centuries. However, the underlying mechanisms of opium tincture are not evident. Aim: To investigate the effects of opium tincture on gastrointestinal motility, intestinal volumes, and water content of different gut segments assessed by magnetic resonance imaging (MRI). Methods: Twenty healthy volunteers were included in a randomized, placebo‐controlled, crossover study of 9 days of treatment with 30 drops of opium tincture per day. MRI was performed on day 1 (before treatment) and day 9 (during treatment). Measurements included assessments of gastric volume, gastric emptying, gastric motility, small bowel volume, small bowel water content, small bowel motility, colon volume, colon water content, and whole gut transit. Key Results: Opium tincture delayed gastric emptying by a mean difference of 5.6 min [95% CI: 1.8–9.4], p = 0.004, and increased postprandial gastric meal volume (17–21%, p = 0.02). Small bowel endpoints did not change. Opium tincture delayed whole gut transit time (p = 0.027) and increased ascending colon volume by 59 mL [95% CI: 15–103], p = 0.004, and transverse colon volume by 48 mL [95% CI: 4–92], p = 0.027. T1‐relaxation time of the descending colon chyme was decreased during opium treatment, indicating dryer feces (difference: −173 ms [95% CI: −336 ‐11], p = 0.03). Conclusion and Inferences: Opium tincture induced changes in the stomach and colon in healthy volunteers. An improved understanding of how opioids affect gut functions may lead to a better understanding and optimized management of diarrhea. [ABSTRACT FROM AUTHOR]

Tramadol is a weak opioid used to treat moderate pain. Stronger opioids inhibit gastrointestinal function, but little is known about the gastrointestinal effects of tramadol. Our aim was to investigate if tramadol causes opioid‐induced bowel dysfunction (OIBD). Twenty healthy male participants (mean age 24 [range 20–31] years) were included. Tramadol (extended‐release formulation, 200 mg/day) or placebo was administered for 10 days in two study periods separated by 3 weeks. Gastrointestinal transit times and segmental volume, motility and water content were investigated with the 3D‐transit system and magnetic resonance imaging. Bowel movements and gastrointestinal symptoms were recorded daily. Tramadol prolonged colonic transit time (34 h vs. 25 h, p < 0.001) and increased small bowel motility (p < 0.01) and water content (p = 0.002) compared to placebo. Across all days of treatment, tramadol reduced the number of mean daily bowel movements (p = 0.001) and increased mean stool consistency (p = 0.006). Gastrointestinal symptom scores increased with tramadol (indigestion: +358%, p = 0.01; constipation: +475%, p = 0.01). Additionally, more participants fulfilled the diagnostic criteria for constipation after tramadol treatment compared to placebo (40% vs. 0%, p < 0.001). This study showed that tramadol treatment is associated with OIBD, and management of constipation and other bowel symptoms should, therefore, be prioritised when treating pain patients with tramadol. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Spinal cord stimulation (SCS) has emerged as a treatment option for patients with chronic pancreatitis (CP) who experience pain that does not respond to standard interventions. However, there is a lack of sham‐controlled trials to support its efficacy. Methods: This randomized, double‐blinded, sham‐controlled, cross‐over trial enrolled 16 CP patients with insufficient pain relief from standard therapies. Patients underwent high‐frequency (1000 Hz) paraesthesia‐free SCS or sham for two 10‐day stimulation periods, separated by a 3‐day washout period. The primary outcome was daily pain intensity registered in a pain diary based on a numeric rating scale (NRS). Secondary outcomes included various questionnaires. Quantitative sensory testing was used to probe the pain system before and after interventions. Results: The average daily pain score on the NRS at baseline was 5.2 ± 1.9. After SCS, the pain score was 4.2 ± 2.1 compared to 4.3 ± 2.1 in the sham group (mean difference −0.1, 95% CI [−1.4 to 1.1]; P = 0.81). Similarly, no differences were observed between groups for the maximal daily pain score, secondary outcomes or quantitative sensory testing parameters. During an open‐label, non‐sham‐controlled and non‐blinded extension of the study, the average daily NRS was 5.2 ± 1.7 at baseline, 3.2 ± 1.8 at 3 months, 2.9 ± 1.9 at 6 months and 3.4 ± 2.2 at 12 months of follow‐up (P = 0.001). Conclusion: In this first sham‐controlled trial of SCS in painful CP, we did not find evidence of short‐term pain relief with paraesthesia‐free high‐frequency (1000 Hz) stimulation. However, evaluation of the long‐term effect by larger sham‐controlled trials with long‐term follow‐up is warranted. Significance Statement: In this first sham‐controlled trial to apply high‐frequency (1000 Hz) spinal cord stimulation in patients with visceral pain due to chronic pancreatitis, we did not find evidence for clinically relevant pain relief. Taken together with potential procedure‐related complications, adverse effects and costs associated with spinal cord stimulation, our findings question its use for management of visceral pain. [ABSTRACT FROM AUTHOR]

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) [ABSTRACT FROM AUTHOR]

Aim To study social disparity in acute pancreatitis (AP) and chronic pancreatitis (CP).We also aimed at exploring whether an interaction exists between alcohol intake and socioeconomic factors. Methods Prospective cohort study based on data from 271 696 men and women participating in the Danish National Health Surveys 2010, and 2013. Information on alcohol and smoking parameters, body mass index (BMI), diet, and education, were self-reported and information on family income was obtained from administrative registers. Outcome variables (acute and chronic pancreatitis) were obtained from national health registers. Results The incidence rate ratio (IRR) of developing AP and CP increased with decreasing family income. Compared to participants in the highest income quintile, participants in the lowest income quintile had 43 (95% CI: 14–80%), 99 (95% CI: 26–214%), and 56% (95% CI: 26–94%) higher incidence rates of AP, CP, and all pancreatitis, respectively. The associations persisted after adjustment for alcohol intake, smoking, BMI, and diet. Likewise, participants with only primary school education had an IRR for an AP of 1.30 (95% CI: 1.06–1.59) compared to those with higher education after adjustment for baseline year, age, and sex. We found no interactions between alcohol intake and income or between alcohol intake and education in relation to neither AP, CP, nor all pancreatitis. Conclusion This large prospective population study showed a significant social disparity in incidence rates of pancreatitis by family income, with higher rates among those with the lowest income and education independent of risk factors such as alcohol intake, smoking, BMI, and diet. [ABSTRACT FROM AUTHOR]