Most patients with disorders of gut-brain interaction receive pharmacotherapy with major or moderate drug-gene interactions.

BACKGROUND: How variations predicted by pharmacogenomic testing to alter drug metabolism and therapeutic response affect outcomes for patients with disorders of gut- brain interaction is unclear. AIMS: To assess the prevalence of pharmacogenomics-predicted drug-gene interactions and symptom outcomes for patients with disorders of gut-brain interaction. METHODS: Patients who were treated in our clinical practice for functional dyspepsia/bowel disorder underwent pharmacogenomic testing. The change in symptoms from baseline to 6 months was compared for patients with variations in CYP2D6 and CYP2C19, which metabolize neuromodulators, and SLC6A4, which encodes the sodium- dependent serotonin transporter. RESULTS: At baseline, 79 of 94 participants (84%) had at least one predicted major drug- gene interaction, and all 94 (100%) had at least one predicted moderate interaction. For the 44 participants who completed a survey of their symptoms at 6 months, the mean (SD) irritable bowel syndrome-symptom severity score decreased from 284 (71) at baseline to 231 (95) at 6 months (p < 0.001). Among patients taking selective serotonin reuptake inhibitors, the decrease in symptom severity (p = 0.03) and pain (p = 0.002) scores from baseline to 6 months was greater for patients with a homozygous SLC6A4 long/long genotype (n = 30) (ie, increased serotonin transporter activity) than for patients with homozygous short/short or heterozygous long/short genotypes (n = 64). Symptom outcomes were not affected by CYP2D6 or CYP2C19 variations. CONCLUSIONS: The homozygous SLC6A4 long/long genotype confers better symptom resolution for patients with disorders of gut-brain interaction who take selective serotonin reuptake inhibitors than do the homozygous short/short or heterozygous long/short genotypes.

Urinary Symptoms and Bladder Voiding Dysfunction Are Common in Young Men with Defecatory Disorders: A Retrospective Evaluation.

BACKGROUND AND AIMS: Lower urinary tract symptoms (LUTS) are frequently reported by constipated patients. Prospective studies investigating the association between defecatory disorders (DDs) and voiding dysfunction, predominantly in women, have reported conflicting results. This study investigated (1) the prevalence of LUTS in young men with DDs and (2) the association between objectively documented DDs and voiding dysfunction in constipated young men with LUTS. METHODS: We reviewed the medical records, including validated questionnaires, of men aged 18-40 with confirmed DDs treated with pelvic floor physical therapy (PT) at our institution from May 2018 to November 2020. In a separate group of constipated young men with LUTS who underwent high-resolution anorectal manometry (HRM), rectal balloon expulsion test (BET), and uroflowmetry, we explored the relationship between DDs and voiding dysfunction. RESULTS: A total of 72 men were evaluated in the study. Among 43 men receiving PT for a proven DD, 82% reported ≥ 1 LUTS, most commonly frequent urination. Over half of these men experienced a reduction in LUTS severity after bowel-directed pelvic floor PT. Among 29 constipated men with LUTS who had undergone HRM/BET and uroflowmetry, 28% had concurrent defecatory and voiding dysfunction, 10% had DD alone, 14% had only voiding dysfunction, and 48% had neither. The presence of DD was associated with significantly increased odds of concurrent voiding dysfunction (odds ratio 9.3 [95% CI 1.7-52.7]). CONCLUSIONS: Most young men with DDs experience LUTS, which may respond to bowel-directed physical therapy. Patients with DD and urinary symptoms have increased odds of voiding dysfunction.

A multicenter study of anorectal pressures and rectal sensation measured with portable manometry in healthy women and men.

BACKGROUND: The equipment and methods for performing anorectal manometry and biofeedback therapy are different and not standardized. Normal values are influenced by age and sex. Our aims were to generate reference values, examine effects of gender and age, and compare anorectal pressures measured with diagnostic and biofeedback catheters and a portable manometry system. METHODS: In this multicenter study, anorectal pressures at rest, during squeeze, and evacuation were measured with diagnostic and biofeedback catheters using Mcompass™ portable device in healthy subjects. Balloon expulsion time and rectal sensation were evaluated. The effects of age and gender were assessed. RESULTS: The final dataset comprised 108 (74 women) of 124 participants with normal rectal balloon expulsion time (less than 60 s). During squeeze, anal resting pressure increased by approximately twofold in women and threefold in men. During evacuation, anal pressure exceeded rectal pressure in 87 participants (diagnostic catheter). The specific rectoanal pressures (e.g., resting pressure) were significantly correlated and not different between diagnostic and biofeedback catheters. With the diagnostic catheter, the anal squeeze pressure and rectal pressure during evacuation were greater in men than women (p ≤ 0.02). Among women, women aged 50 years and older had lower anal resting pressure; rectal pressure and the rectoanal gradient during evacuation were greater in older than younger women (p ≤ 0.01). CONCLUSIONS: Anal and rectal pressures measured with diagnostic and biofeedback manometry catheters were correlated and not significantly different. Pressures were influenced by age and sex, providing reference values in men and women.

Patient-oriented education and visual-aid intervention are inadequate to identify patients with potential capsule retention: a prospective randomized study.

Background/aims: The key procedure-related risk with video capsule endoscopy (VCE) is capsule retention, which should be suspected in patients who have not reported capsule passage. The study aims were to determine the frequency of capsule passage visualization and the difference in self-reporting of capsule passage between patients who receive patient-oriented education (POE) and patients who receive POE and a visual aid intervention in the form of a wrist band (WB). Methods: This was a prospective randomized study that enrolled patients undergoing VCE. Patients were randomly assigned to a POE group versus a POE and WB group. POE consisted of verbal education and an information booklet. Both groups received instructions to notify the study team regarding capsule passage. Results: Sixty patients (mean age 57 ± 18 years; 61% female) were included. A total of 57 patients were included in the analysis (3 lost to follow-up; 28 in POE group; 29 in WB group). Capsule passage status was reported by 68% without significant difference between POE and WB groups (72% vs. 64%; p = .51). Capsule passage status was obtained from all 57 patients with the addition of a proactive follow-up. Only 56% (n = 32) reported visualizing capsule passage. Of the remaining patients who did not visualize capsule passage, 60% (n = 15) reported on this without significant difference between the POE and WB groups (p = .23). Conclusions: Lack of visualization of capsule passage is a poor indicator of retention. Self-reporting of VCE passage status is suboptimal and the addition of a visual aid did not improve this parameter.

Characterization of Upper Gastrointestinal Symptoms, Gastric Motor Functions, and Associations in Patients with Diabetes at a Referral Center.

OBJECTIVES: Our aim was to characterize upper gastrointestinal (UGI) symptoms and associations in individuals with diabetes mellitus (DM) who had undergone evaluation of gastric emptying (GE) and accommodation (GA) at a referral center. METHODS: From the Mayo Clinic Rochester electronic medical records of adults with diabetes types 1 and 2 (DM1 and DM2) evaluated between January 1997 and December 2015, we extracted demographics, UGI symptoms, current medications, treatments for diabetes, GE solids by scintigraphy, GA by single photon emission computed tomography (SPECT), and diabetes complications. We compared subgroups with delayed (GE at 2 h <25% or GE at 4 h <75%), rapid (GE at 1 h > 35%), and normal GE, as well as reduced (<428 mL) and normal GA. RESULTS: We reviewed 108 patients (60.2% females, median age 49.0 years). Overall, 71.3% had DM2; one-third of these were insulin dependent and had fairly well-controlled diabetes (median HbA1c 6.7% (IQR 6.2; 7.9)). Manifestations of diabetic triopathy (peripheral neuropathy, nephropathy, and retinopathy) were uncommon at presentation with UGI symptoms. Nausea was the most common symptom (80.6%). There were single or combined GE (total 56%: rapid in 37%, slow in 19%) and GA (total 39%) abnormalities; there was normal GA and GE in 28%; 40.3% of the DM2 patients had accelerated GE at 1 h. GE at 1 h is associated with nausea/vomiting, and fasting gastric volume is associated with bloating. CONCLUSIONS: Among referred diabetic patients with UGI symptoms, GE and GA testing identifies potential targets for individualizing treatment and avoidance of empirical trials for the 28% with no disturbance of GE and GA.

Evaluation of Patients with Suspected Gastroparesis.

There is substantial overlap between the symptoms of gastroparesis and a variety of alternative disorders. These conditions include rumination syndrome, drug-induced gastric emptying delay, cannabinoid hyperemesis syndrome, and eating disorders, which can be identified based on the history alone. The remaining patients require a diagnostic approach of physical examination, laboratory tests, evaluation with esophagogastroduodenoscopy or contrast radiography, and a test to measure gastric emptying. Symptomatic patients who have normal nutritional status and gastric emptying that is either normal or mildly delayed should be diagnosed with functional dyspepsia, whereas patients with moderate or severe gastric emptying delay are diagnosed with gastroparesis.

Gastric Motor Dysfunction in Patients With Functional Gastroduodenal Symptoms.

OBJECTIVES: The pathophysiology of dyspeptic symptoms is complex. The aim of this study was to evaluate the association of gastric emptying (GE), gastric accommodation (GA), and respiratory sinus arrhythmia (RSA, to assess vagal dysfunction) in a large cohort with functional gastroduodenal symptoms. METHODS: We reviewed demographic, clinical features, and results of gastric motor and vagal function studies of 1,287 patients (74.0% females, mean age 43.1±15.4 years) who had undergone both single photon emission computed tomography GA and scintigraphic GE. Accommodation was based on postprandial to fasting gastric volume ratio (VR). Electrocardiograms were available and analyzed for RSA in 300 patients. RESULTS: There were 29.8% patients with normal GE and GA, 21.9% with abnormal GA only, 27.1% with abnormal GE only, and 21.1% with abnormal GA and GE. There were numerical differences in GA among patients with normal, accelerated, and delayed GE (P=0.062, by χ2). Increased GA (VR >3.85) was more prevalent in patients with delayed GE compared to accelerated GE (14.0% vs. 6.8%, P=0.004). Decreased VRs (median 2.9) were observed with accelerated GE compared to normal GE (median 3.1, P<0.05). Nausea and vomiting were more prevalent (in contrast to the less prevalent bloating) in patients with delayed compared to accelerated or normal GE (all P<0.05). In patients with diminished RSA, there was higher prevalence of reduced GA (41.5%) compared to those with preserved RSA (29.2%, P=0.031). Multivariable analysis showed associations of the main abdominal symptoms with gender, body mass index, gastric emptying, diabetes, and prior abdominal surgery. CONCLUSIONS: Patients with symptoms of functional gastroduodenal disorders may have one or more gastric motor dysfunctions and reduced RSA; among the patients with abnormal gastric motor functions, vomiting suggests delayed GE, whereas reduced RSA is associated with reduced GA.

Polymorphisms of 5-HTT LPR and GNß3 825C>T and Response to Antidepressant Treatment in Functional Dyspepsia: A Study from The Functional Dyspepsia Treatment Trial.

OBJECTIVES: The Functional Dyspepsia Treatment Trial reported that amitriptyline (AMI) was associated with adequate relief of functional dyspepsia (FD) symptoms, but the pharmacogenetics of antidepressant response in FD are not known. GNß3 825C>T CC genotype has been previously linked to FD and TT genotype to antidepressant response in depression. The ss genotype of the 5-HTT LPR variant of the serotonin transporter gene (SLC6A4) has been linked to selective serotonin reuptake inhibitor (SSRI) response. We aimed to examine whether GNß3 825C>T and 5-HTT LPR polymorphisms result in differential treatment effects in FD patients receiving antidepressant therapy. METHODS: Participants were randomized to receive placebo, 50 mg AMI, or 10 mg escitalopram (ESC). The primary end point was adequate relief for ≥5 weeks of the last 10 weeks. Genotyping of GNß3 825C>T and 5-HTT LPR was performed utilizing PCR-based methods. RESULTS: GNß3 825C>T and 5-HTT LPR genotype data were available for 256 (88%) and 246 (84%) patients, respectively. Both polymorphisms were in Hardy-Weinberg equilibrium. In tests for differential treatment, neither 5-HTT LPR nor GNß3 825C>T genotype influenced response to therapy (P=0.89 and P=0.54, respectively). Although there was a tendency for a more favorable response to ESC in the SS/LS genotype compared to the LL genotype groups (40% vs. 31% reporting adequate relief of FD symptoms) among those in the ESC treatment arm, this was not significant (P=0.43). CONCLUSIONS: GNß3 825C>T and 5-HTT LPR genetic variants do not alter treatment response to tricyclic and SSRI antidepressants in FD.

Effects of Rifaximin on Transit, Permeability, Fecal Microbiome, and Organic Acid Excretion in Irritable Bowel Syndrome.

OBJECTIVES: Rifaximin relieves irritable bowel syndrome (IBS) symptoms, bloating, abdominal pain, and loose or watery stools. Our objective was to investigate digestive functions in rifaximin-treated IBS patients. METHODS: In a randomized, double-blind, placebo-controlled, parallel-group study, we compared the effects of rifaximin, 550 mg t.i.d., and placebo for 14 days in nonconstipated IBS and no evidence of small intestinal bacterial overgrowth (SIBO). All subjects completed baseline and on-treatment evaluation of colonic transit by scintigraphy, mucosal permeability by lactulose-mannitol excretion, and fecal microbiome, bile acids, and short chain fatty acids measured on random stool sample. Overall comparison of primary response measures between treatment groups was assessed using intention-to-treat analysis of covariance (ANCOVA, with baseline value as covariate). RESULTS: There were no significant effects of treatment on bowel symptoms, small bowel or colonic permeability, or colonic transit at 24 h. Rifaximin was associated with acceleration of ascending colon emptying (14.9±2.6 h placebo; 6.9±0.9 h rifaximin; P=0.033) and overall colonic transit at 48 h (geometric center 4.0±0.3 h placebo; 4.7±0.2 h rifaximin; P=0.046); however, rifaximin did not significantly alter total fecal bile acids per g of stool or proportion of individual bile acids or acetate, propionate, or butyrate in stool. Microbiome studies showed strong associations within subjects, modest associations with time across subjects, and a small but significant association of microbial richness with treatment arm (rifaximin vs. treatment). CONCLUSIONS: In nonconstipated IBS without documented SIBO, rifaximin treatment is associated with acceleration of colonic transit and changes in microbial richness; the mechanism for reported symptomatic benefit requires further investigation.

Innovative gastric endoscopic muscle biopsy to identify all cell types, including myenteric neurons and interstitial cells of Cajal in patients with idiopathic gastroparesis: a feasibility study (with video).

BACKGROUND AND AIMS: The pathophysiology of some GI neuromuscular diseases remains largely unknown. This is in part due to the inability to obtain ample deep gastric wall biopsies that include the intermuscular layer of the muscularis propria (MP) to evaluate the enteric nervous system, interstitial cells of Cajal (ICCs), and related cells. We report on a novel technique for gastric endoscopic muscle biopsy (gEMB). METHODS: Patients with idiopathic gastroparesis were prospectively enrolled in a feasibility study by using a novel "no hole" gEMB. Main outcome measures were technical success, adverse events, and histologic confirmation of the intermuscular layer, including myenteric neurons and ICC. The gEMB was a double resection clip-assist technique. A site was identified on the anterior wall of the gastric body as recommended by the International Working Group on histologic techniques. EMR was performed to unroof and expose the underlying MP. The exposed MP was then retracted into the cap of an over-the-scope clip. The clip was deployed, and the pseudopolyp of MP created was resected. This resulted in a no-hole gEMB. RESULTS: Three patients with idiopathic gastroparesis underwent gEMB. Patients had severe delayed gastric emptying with a mean (± standard deviation [SD]) of 49 ± 16.8% of retained gastric contents at 4 hours. They had no history of gastric or small-bowel surgery and did not use steroids or other immunosuppressive drugs. The gEMB procedure was successfully performed, with no procedural adverse events. Postprocedural abdominal pain was controlled with nonsteroidal anti-inflammatory agents and opioid analgesics. Mean length of resected MP was 10.3 ± 1.5 mm. Mean procedure time was 25.7 ± 6 minutes. Hematoxylin and eosin (H&E) staining of tissue samples confirmed the presence of both inner circular and outer longitudinal muscle, as well as the intermuscular layer. H&E staining showed reduced myenteric ganglia in 1 patient. In 2 patients, specialized immunohistochemistry was performed, which showed a marked decrease in myenteric neurons as delineated by an antibody to protein gene product 9.5 and a severe decrease in ICC levels across the muscle layers. At 1 month follow-up, upper endoscopy showed a well-healed scar in 2 patients and minimal ulceration with a retained clip in 1 patient. CT of the abdomen confirmed the integrity of the gastric wall in all patients. Because of lack of an immune infiltrate in the resected samples, patients were not considered suitable for immunosuppressive or steroid therapy. CONCLUSIONS: gEMB is feasible and easy to perform, with acquisition of tissue close to surgical samples to identify myenteric ganglia, ICCs, and multiple cell types. The ability to perform gEMB represents a paradigm shift in endoscopic tissue diagnosis of gastric neuromuscular pathologies.

A Pilot Study of the Effect of Daikenchuto on Rectal Sensation in Patients with Irritable Bowel Syndrome.

BACKGROUND/AIMS: Daikenchuto (TU 100), a botanical agent that modulates gastrointestinal nerves, is used in the treatment of motility and functional disorders. Our aim was to study the effects of TU-100 on rectal compliance and sensation in patients with irritable bowel syndrome (IBS). METHODS: In 20 patients per treatment arm, we conducted a single-center, randomized, parallel-group, double-blind, placebo-controlled, single-dose pharmacodynamics study evaluating the effects of TU-100, 15 g (5 g t.i.d. [means 3 times a day]), for 14-16 consecutive days on rectal compliance and rectal sensation (thresholds and sensation ratings), all measured at baseline and on the last day of medication treatment. The primary endpoint was rectal sensation thresholds and sensation ratings in response to balloon distension at 32 mmHg. Secondary endpoints were rectal compliance, sensation thresholds, ratings and tone (fasting and postprandial), bowel pattern, abdominal pain (average and worst severity) and bloating scores, IBS quality of life and safety profile. RESULTS: Rectal sensation ratings post-treatment were significantly associated with baseline (pre-treatment) ratings and with level of anxiety or stress recorded at the time of the sensation testing. There were no effects of TU-100 treatment on rectal sensation ratings, sensation thresholds, rectal fasting or postprandial tone, rectal compliance, bowel function, abdominal pain or bloating scores, or IBS quality of life. CONCLUSIONS: TU-100 did not significantly affect rectal compliance and sensation in patients with IBS in this study.

Relamorelin Relieves Constipation and Accelerates Colonic Transit in a Phase 2, Placebo-Controlled, Randomized Trial.

BACKGROUND & AIMS: Ghrelin receptors are located in the colon. Relamorelin is a pentapeptide selective agonist of ghrelin receptor 1a with gastric effects, but its effects in the colon are not known. We aimed to evaluate the effects of relamorelin on bowel movements (BMs) and gastrointestinal and colonic transit (CT) in patients with chronic constipation. METHODS: We performed a study of 48 female patients with chronic constipation who fulfilled the Rome III criteria and had 4 or fewer spontaneous BMs (SBMs)/wk. In a randomized (1:1), double-blind, parallel-group, placebo-controlled trial, the effects of relamorelin (100 µg/d, given subcutaneously) were tested during 14 days after a 14-day baseline, single-blind phase in which patients were given placebo at 2 Mayo Clinic sites. The participants' mean age was 40.6 ± 1.5 y, with a mean body mass index of 25.7 ± 0.6 kg/m(2), with 1.7 ± 0.1 SBM/wk, and a mean stool consistency of 1.2 ± 0.1 on the Bristol scale during this baseline period. The effect of treatment on transit was measured in 24 participants with colonic transit of less than 2.4 (geometric center at 24 h) during the baseline period. Gastric emptying, small-bowel transit, and CT were measured during the last 2 days that patients received relamorelin or placebo. Bowel function was determined from daily diaries kept by patients from days 1 through 28. Study end points were time to first BM, SBMs/wk, complete SBMs/wk, stool form, and ease of stool passage. Effects of relamorelin were assessed by analysis of covariance. RESULTS: Compared with placebo, relamorelin accelerated gastric emptying half-time (P = .027), small-bowel transit (P = .051), and CT at 32 hours (P = .040) and 48 hours (P = .017). Relamorelin increased the number of SBMs (P < .001) and accelerated the time to first BM after the first dose was given (P = .004) compared with placebo, but did not affect stool form. Adverse events associated with relamorelin included increased appetite, fatigue, and headache. CONCLUSIONS: Relamorelin acts in the colon to significantly reduce symptoms of constipation and accelerate CT in patients with chronic constipation, compared with placebo. ClinicalTrial.Gov registration number: NCT01781104.

Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: A Multicenter, Randomized Controlled Study.

BACKGROUND & AIMS: Antidepressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or postprandial fullness. However, there is little evidence of the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms, gastric emptying (GE), and meal-induced satiety in patients with FD. METHODS: We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants. Patients (n = 292; 44 ± 15 years old, 75% were female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (of 12). Secondary end points included GE time, maximum tolerated volume in Nutrient Drink Test, and FD-related quality of life. RESULTS: An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) (P = .05, after treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief than those given placebo (odds ratio = 3.1; 95% confidence interval: 1.1-9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio = 0.4; 95% confidence interval: 0.2-0.8). Both antidepressants improved overall quality of life. CONCLUSIONS: Amitriptyline, but not escitalopram, appears to benefit some patients with FD, particularly those with ulcer-like (painful) FD. Patients with delayed GE do not respond to these drugs. ClinicalTrials.gov ID: NCT00248651.

Endoscopic full-thickness biopsy of the gastric wall with defect closure by using an endoscopic suturing device: survival porcine study.

BACKGROUND: The pathogenesis of several common gastric motility diseases and functional GI disorders remains essentially unexplained. Gastric wall biopsies that include the muscularis propria to evaluate the enteric nervous system, interstitial cells of Cajal, and immune cells can provide important insights for our understanding of the etiology of these disorders. OBJECTIVES: To determine the technical feasibility, reproducibility, and safety of performing a full-thickness gastric biopsy (FTGB) by using a submucosal endoscopy with mucosal flap (SEMF) technique; the technical feasibility, reproducibility, and safety of tissue closure by using an endoscopic suturing device; the ability to identify myenteric ganglia in resected specimens; and the long-term safety. DESIGN: Single center, preclinical survival study. SETTING: Animal research laboratory, developmental endoscopy unit. SUBJECTS: Twelve domestic pigs. INTERVENTIONS: Animals underwent an SEMF procedure with gastric muscularis propria resection. The resultant offset mucosal entry site was closed by using an endoscopic suturing device. Animals were kept alive for 2 weeks. MAIN OUTCOME MEASUREMENTS: The technical feasibility, reproducibility, and safety of the procedure; the clinical course of the animals; the histological and immunochemical evaluation of the resected specimen to determine whether myenteric ganglia were present in the sample. RESULTS: FTGB was performed by using the SEMF technique in all 12 animals. The offset mucosal entry site was successfully closed by using the suturing device in all animals. The mean resected tissue specimen size was 11 mm. Mean total procedure time was 61 minutes with 2 to 4 interrupted sutures placed per animal. Histology showed muscularis propria and serosa, confirming full-thickness resections in all animals. Myenteric ganglia were visualized in 11 of 12 animals. The clinical course was uneventful. Repeat endoscopy and necropsy at 2 weeks showed absence of ulceration at both the mucosal entry sites and overlying the more distal muscularis propria resection sites. There was complete healing of the serosa in all animals with minimal single-band adhesions in 5 of 12 animals. Retained sutures were present in 10 of 12 animals. LIMITATIONS: Animal experiment. CONCLUSIONS: FTGB by using the SEMF technique and an endoscopic suturing device is technically feasible, reproducible, and safe. Larger tissue specimens will allow improved analysis of multiple cell types.

Methods for the assessment of small-bowel and colonic transit.

Transit assessment of the small intestine and colon is relevant in the study of physiology, pathophysiology, and pharmacodynamics, and there is increasing use of small-bowel and colonic transit measurements in clinical practice as well. The main methods that are applied in clinical practice are substrate-hydrogen breath tests for small-bowel transit and radiopaque markers for colonic transit. Over the past 2-3 decades, scintigraphy has become the preferred standard in research studies, particularly for studies of pathophysiology and pharmacodynamics. New approaches include experimental stable isotope measurement of orocecal transit and the recently approved method using a wireless motility capsule that is validated as an accurate measurement of small-bowel and colonic transit.