Consistency of Feces Affects Defecatory Function.

Background/Aims: It is a common belief that constipated patients have hard feces that contributes to the difficulties defecating. To the best of our knowledge, no studies had been published on controlled evacuation of simulated feces with different consistencies. Methods: Twelve normal subjects were recruited for studies with the simulated feces device "Fecobionics" of different consistency (silicone shore 0A-40A corresponding to Bristol Stool Form Scale types 2-4). The subjects filled out questionnaires and had the balloon expulsion test (BET) and anorectal manometry (ARM) done for reference. The Fecobionics probes were inserted in rectum in random order with +20 minutes between insertions. The bag was filled to urge-to-defecate and evacuations took place in privacy. Non-parametric statistics with median and quartiles are provided. Results: One subject was excluded due to technical issues, and another had abnormal ARM-BET. The 4 females/6 males subjects were 23yrs (range 20-48). Most differences were observed between the 0A and 10A probe (duration, maximum bag pressure, duration x maximum bag pressure, and relaxation of the front pressure and the bend angle during evacuation), eg, the duration was 9 (8-12) seconds at 0A and 18 (12-21) seconds at 10A (P < 0.05), and maximum bag pressure was 107 (96-116) at 0A and 140 (117-162) cmH2O at 10A (P < 0.05). The bend angle before evacuation differed between the probes whereas only the 10A differed from 40A during defecation. The 10A was harder to evacuate than the 0A probe. Except for the bend angles, no further significant change was observed from 10A to 40A. Conclusion: Fecal consistency affects defecatory parameters.

The rectum, anal sphincter and puborectalis muscle show different contraction wave forms during prolonged measurement with a simulated feces.

Contractile patterns in rectum, puborectalis muscle and anal sphincter must be studied to understand defecation. Six subjects had contractile waveforms studied with Fecobionics. Symptom questionnaires, balloon expulsion test and anorectal manometry were done for reference. The Fecobionics bag was filled in rectum to urge-to-defecate volume and measurements were done for 4 h before the subjects attempted to evacuate the device. Pressures and bend angle (BA) variations were analyzed with Fast Fourier Transformation. Four normal subjects exhibited low frequency waves (< 0.06 Hz) for pressures and BA. The waves were uncoordinated between recordings, except for rear and bag pressures. Peak wave amplitudes occurred at 0.02-0.04 Hz. Pressures and the BA differed for peak 1 (p < 0.001) and peak 2 amplitudes (p < 0.005). The front pressure amplitude was bigger than the others (rear and BA, p < 0.05; bag, p < 0.005) for peak 1, and bigger than bag pressure (p < 0.005) and BA (p < 0.05) for peak 2. One subject was considered constipated with lower front pressure amplitudes compared to normal subjects and increased amplitudes for other parameters. The sixth subject was hyperreactive and differed from the other subjects. In conclusion, the rectum, anal sphincter and puborectalis muscle showed different contraction waves during prolonged measurements. The data call for larger studies to better understand normal defecation, feces-withholding patterns, and the implications on anorectal disorders.

Redefine the role of d-α-Tocopheryl polyethylene glycol 1000 succinate on P-glycoprotein, multidrug resistance protein 1, and breast cancer resistance protein mediated cancer multidrug resistance.

Cancer drug resistance is an ever-changing problem that most patients need to face in their later stages of treatment, especially the multidrug resistant (MDR) type. The drug efflux transporters, including P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP), play the crucial roles in this sophisticated battle. In recent decades, researchers try to find potential inhibitors to impede the drug efflux function of above transporters. d-α-Tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is a prevalently used excipient in the formulation design. In the present study, the modulatory effects and mechanisms of vitamin E TPGS on the efflux transporters were investigated. And the cancer MDR reversing ability of vitamin E TPGS was evaluated as well. Stable-cloned transporter over-expressed cell lines were used for mechanisms study, while several types of MDR cancer cell lines were adopted as reversing evaluation models. The results exhibited that vitamin E TPGS significantly inhibited the efflux function of P-gp, MRP1, and BCRP under non-cytotoxic concentrations, but not influencing the protein expression levels. Through efflux assay and molecular docking, vitamin E TPGS was found to be an uncompetitive, non-competitive, and competitive inhibitor on chemotherapeutic drug doxorubicin efflux in P-gp, MRP1, and BCRP over-expressing cell lines, respectively. Furthermore, the basal ATPase activity of three transporters were significantly inhibited by vitamin E TPGS at 10 µM. And the cell membrane fluidity of P-gp over-expressing cell line was enhanced by 22.58% with 5 µM vitamin E TPGS treatment, compared to the parental Flp-In™-293 cell line (without P-gp). The resistance reversing ability of vitamin E TPGS was prominent in MCF-7/DOX MDR breast cancer cell line, which over-expressed P-gp, MRP1, and BCRP. These significant results suggested that vitamin E TPGS is a promising modulator on transporters mediated cancer MDR. Vitamin E TPGS is not an inert excipient, but possesses MDR-reversing pharmacological effects, and deserves a re-purposing application on the future combinatorial regimen design for MDR cancer treatment.

Defecatory Function Studies Using the Fecobionics Device Are Repeatable.

BACKGROUND: Only limited data exist on repeatability of anorectal studies with the established physiological and clinical technologies for assessment of anorectal function. Fecobionics is a new multi-sensor simulated feces that provide data by integrating elements from current tests. AIMS: To study repeatability of anorectal data obtained with the Fecobionics device. METHODS: We assessed the database of Fecobionics studies to determine how many repeated studies were done. From a total of 260 Fecobionics studies, 19 subjects with repeated studies using approximately the same protocol and prototype were identified. Key pressure and bending parameters were assessed and the repeatability analyzed using Bland Altman plots. Furthermore, the inter- and intra-individual coefficient of variation (CV) were computed. RESULTS: Fifteen subjects (5F/10 M) with repeated studies were normal subjects, three were patients with fecal incontinence and one subject suffered from chronic constipation. The main analysis was conducted on the cohort of normal subjects. The bias for 11 parameters were within the confidence interval, whereas two were slightly outside. The interindividual CV was lowest for the bend angle (10.1-10.7) and between 16.3 and 51.6 for the pressure parameters. The intra-individual CVs were approximately half of the inter-individual CVs, spanning from 9.7 to 27.6. CONCLUSION: All data from normal subjects were within previously defined normality. The Fecobionics data showed acceptable repeatability with bias within the confidence limits for almost all parameters. The intra-individual CV was much lower than the inter-individual CV. Dedicated large-scale studies are warranted to evaluate the influence of age, sex, and disease on repeatability as well as comparing between technologies.

Fecobionics characterization of female patients with fecal incontinence.

Defecatory disorders including fecal incontinence (FI) are diagnosed on the symptom pattern supplemented by anorectal manometry (ARM), the balloon expulsion test (BET), and endo-anal ultrasonography. In this study, we used a simulated stool named Fecobionics to study distinct defecation patterns in FI patients using preload-afterload diagrams and to provide comparative data on defecation indices (DIs) between passive and urge incontinent patients. All subjects had Fecobionics, endo-anal ultrasonography and ARM-BET done. The Fecobionics bag was distended in rectum until urge in 37 female patients (64.1 ± 1.5 yrs) and a group of normal subjects (NS, 12F, age 64.8 ± 2.8 yrs). Rear-front pressure (preload-afterload) diagrams and DIs were compared between groups. The FISI score in the patients was 8.6 ± 0.6. The NS did not report FI-related symptoms. All patients and NS defecated Fecobionics and ARM-BET within 2 min. The urge volume was 46.1 ± 3.6 and 35.3 ± 5.9 mL in the FI and normal groups (P > 0.1). The expulsion duration was 14.8 ± 2.4 and 19.8 ± 5.1 s for the two groups (P > 0.1). The preload-afterload diagrams demonstrated clockwise loops that clearly differed between the FI subtypes and NS. The DIs showed profound difference between patients and NS. Fecobionics data showed higher correlation with symptoms in FI patients than ARM-BET. Fecobionics obtained novel pressure signatures in subtypes of FI patients and NS. Fecobionics provides DI data that cannot be obtained with ARM-BET.

Fecobionics Evaluation of Biofeedback Therapy in Patients With Fecal Incontinence.

INTRODUCTION: Biofeedback therapy (BFT) is a well-known treatment for functional anorectal disorders. The effect of BFT was monitored in fecal incontinence (FI) patients with the Fecobionics test and with the conventional technologies, anorectal manometry (ARM) and balloon expulsion test (BET). METHODS: Studies were performed in 12 patients before and after 8 weeks of biofeedback training. The Fecal Incontinence Severity Index (FISI) score was obtained. Anal resting and squeeze pressures were measured before the bag was distended in the rectum until urge to defecate. Pressure recordings were made during Fecobionics evacuation. RESULTS: BFT resulted in 24% reduction in FISI scores (P < 0.01). Seven patients were characterized as responders. Anal pressures, the urge-to-defecate volume, and defecatory parameters did not change significantly during BFT. For ARM-BET, the maximum anal squeeze pressure, the urge-to-defecate volume, and the expulsion time were lower after BFT compared with those before BFT (P < 0.05). For Fecobionics, the change in urge volume (r = 0.74, P < 0.05) and the change in defecation index (r = 0.79, P < 0.01) were associated with the change in FISI score. None of the ARM-BET parameters were associated with the change in FISI score. It was studied whether any pre-BFT data could predict treatment success. The Fecobionics expulsion duration and the defecation index predicted the outcome (P < 0.05). The defecation index had a sensitivity of 100% and a specificity of 72%. None of the ARM-BET parameters predicted the outcome (all P > 0.2). DISCUSSION: Fecobionics was used as a tool to monitor the effect of BFT and proved better than conventional technologies for monitoring and predicting the outcome in the FISI score.

Functional anorectal studies in patients with low anterior resection syndrome.

BACKGROUND: Most patients who have undergone low anterior resection suffer from bowel dysfunction postoperatively. This condition is referred to as low anterior resection syndrome (LARS). The aim was to study defecatory patterns in LARS patients compared to a primary control group of fecal incontinence (FI) patients and normal subjects (NS) with the Fecobionics device. METHODS: Fecobionics expulsion parameters were assessed in an interventional study design. The Fecobionics probe contained pressure sensors at the front, rear, and inside the bag. The bag was distended until urge sensation in rectum in 11 LARS patients (5F/6M, 63.2 ± 2.9 years), 11 FI subjects (7F/4M, 64.4 ± 2.5 years), and 11 NS (7F/4M, 63.6 ± 3.0 years). Defecation indices were computed from the Fecobionics data. All subjects had high-resolution anorectal manometry (ARM) and balloon expulsion test (BET) done. Symptoms were evaluated with LARS and Wexner scores. KEY RESULTS: The LARS score in the LARS patients was 39.0 ± 0.6. The Wexner score in the LARS, FI, and NS groups was 14.2 ± 0.7, 10.1±1.0, and 0.0 ± 0.0 (p < 0.01). The resting anal pressure and squeeze pressure were lowest in LARS patients (p < 0.05). The urge volume was 11.8 ± 4.2, 59.6 ± 6.4, and 41.6 ± 6.4 ml in the LARS, FI, and NS groups, respectively (p < 0.001). The expulsion duration did not differ between groups. Defecation indices were lowest in the LARS patients (p < 0.05). ARM-BET confirmed the low urge volume in LARS patients whereas anal pressures did not differ between groups. CONCLUSIONS AND INFERENCES: The LARS patients had low anal pressures and urge volume. Most Defecation Indices differed between the LARS group and the other groups.

Characterization of Patients With Obstructed Defecation and Slow Transit Constipation With a Simulated Stool.

INTRODUCTION: Defecatory disorders including obstructed defecation (OD) are currently diagnosed using specialized investigations including anorectal manometry and the balloon expulsion test. Recently, we developed a simulated stool named Fecobionics that provides a novel type of pressure measurements and analysis. The aim was to study OD phenotypes compared with slow transit constipation (STC) patients and normal subjects (NS). METHODS: Fecobionics expulsion parameters were assessed in an interventional study design. The Fecobionics device contained pressure sensors at the front, rear, and inside a bag. All constipation patients had colon transit study, defecography, anorectal manometry, and balloon expulsion test performed. The Fecobionics bag was distended in the rectum until desire-to-defecate in 26 OD compared with 8 STC patients and 10 NS. Rear-front pressures (preload-afterload parameters) and defecation indices (DIs) were compared between groups. RESULTS: The Wexner constipation scoring system score was 13.8 ± 0.9 and 14.6 ± 1.5 in the OD and STC patients (P > 0.5). The median desire-to-defecate volume was 80 (quartiles 56-80), 60 (54-80), and 45 (23-60) mL in OD, STC, and NS, respectively (P < 0.01). The median expulsion duration was 37 (quartiles 15-120), 6 (3-11), and 11 (8-11) seconds for the 3 groups (P < 0.03). Fecobionics rear-front pressure diagrams demonstrated clockwise loops with distinct phenotype differences between OD and the other groups. Most DIs differed between OD and the other groups, especially those based on the anal afterload reflecting the nature of OD constipation. Several OD subtypes were identified. DISCUSSION: Fecobionics obtained novel pressure phenotypes in OD patients. DIs showed pronounced differences between groups. Larger studies are needed on OD subtyping.

Mechanophysiological analysis of anorectal function using simulated feces in human subjects.

INTRODUCTION: Defecation is a complex process that is difficult to study and analyze. OBJECTIVES: Here, we present new analytical tools to calculate frictional force and tension during expulsion of the Fecobionics simulated stool in human subjects. METHODS: The 12-cm-long Fecobionics device contained pressure sensors, motion processor units for measurement of orientation and bending, and impedance rings for measurement of cross-sectional areas. Eight normal subjects defecated Fecobionics. The bending angle of the device, frictional force between the device and the surrounding tissue, and the stretch tensions were calculated. RESULTS: The bending angle and pressures changed during expulsion with the maximum pressure recorded at the rear. The averaged circumferential tension, longitudinal tension and friction force in each subject were associated with the front-rear pressure difference (r > 0.7, p < 0.005). The peak circumferential tension, longitudinal tension, and friction force immediately before expulsion of the rear were significantly higher compared to when the front entered the anal canal (F = 164.7, p < 0.005; F = 152.1, p < 0.005; F = 71.4, p < 0.005; respectively.). CONCLUSION: This study shows that Fecobionics obtained reliable data under physiological conditions. Mechanical features such as frictional force and stretch tensions were assessable during Fecobionics expulsion.

Fecobionics Characterization of Patients With Fecal Incontinence.

Fecal incontinence (FI) is characterized by involuntary loss of rectal content. Up to 9.5% of Americans younger than 70 years suffer from FI.1 The pathophysiology has many causes and is not well understood and diagnosed.

Simulated stool for assessment of anorectal physiology.

Fecal continence is maintained by several mechanisms including anatomical factors, anorectal sensation, rectal compliance, stool consistency, anal muscle strength, mobility, and psychological factors. The homeostatic balance is easily disturbed, resulting in symptoms including fecal incontinence and constipation. Current technologies for assessment of anorectal function have limitations. Overlap exist between data obtained in different patient groups, and there is lack of correlation between measurements and symptoms. This review describes a novel technology named Fecobionics for assessment of anorectal physiology. Fecobionics is a simulated stool, capable of dynamic measurements of a variety of variables during defecation in a single examination. The data facilitate novel analysis of defecatory function as well as providing the foundation for modeling studies of anorectal behavior. The advanced analysis can enhance our physiological understanding of defecation and future interdisciplinary research for unraveling defecatory function, anorectal sensory-motor disorders, and symptoms. This is a step in the direction of improved diagnosis of anorectal diseases.

Novel Fecobionics Defecatory Function Testing.

INTRODUCTION: Defecation is a complex process that can be easily disturbed. Defecatory disorders may be diagnosed using specialized investigation, including anorectal manometry (ARM) and the balloon expulsion test (BET). Recently, we developed a simulated stool named Fecobionics that integrates several tests and assesses pressures, orientation, and bending during evacuation. The aim was to evaluate the feasibility and performance of Fecobionics for assessing defecatory physiology in normal subjects. METHODS: Physiological expulsion parameters were assessed in an interventional study design. The 10-cm-long Fecobionics probe contained pressure sensors at the front and rear and inside a bag and 2 motion processor units. The bag was distended in the rectum of 20 presumed normal subjects (15 female/5 male) until urge to defecate. ARM-BET was also performed. Three subjects used +2 minutes to evacuate BET, and 1 subject had a high fecal incontinence score. Therefore, the normal group consisted of 16 subjects (13 female/3 male aged 25-78 years). RESULTS: All subjects reported that Fecobionics evacuation was similar to normal defecation. Fecobionics expulsion pressure signatures demonstrated 5 phases, reflecting rectal pressure, anal relaxation, and anal passage. Preload-afterload loop diagrams demonstrated clockwise contraction cycles. The expulsion duration for BET and Fecobionics was 16 ± 2 and 23 ± 5 seconds (P > 0.2), respectively. The duration of the Fecobionics and BET expulsions was associated (P < 0.001). The change in bending of Fecobionics during defecation was 40 ± 3°. DISCUSSION: Fecobionics obtained reliable data under physiological conditions. Agreement was found for comparable variables between ARM-BET and Fecobionics but not for other variables. The study suggests that Fecobionics is safe and effective in evaluation of key defecatory parameters.