Background Gastric electrical stimulation (GES) represents a new therapy in patients with intractable vomiting and nausea. We aimed to determine preoperative factors associated with positive response ...during GES. Thirty-three consecutive patients received implants for medically refractory nausea or vomiting or both. Study Design Symptoms, Quality of Life (QOL), and gastric emptying (GE) were monitored before and 6 months after implantation. Compared with baseline, dyspeptic symptoms including nausea and vomiting, and QOL all improved at 6 months, yielding a significant weight gain while the GE rate remained unchanged. Twenty-four patients reported improvement; nine remained unimproved at 6 months. Results In multivariate analysis, baseline QOL and appetite alterations were predictive of improvement; previous history of gastric surgery was associated with failure. Surprisingly, patients with initial delayed GE (21 of 33) displayed similar improvement compared with patients with normal GE. Likewise, basal GE was not found to be predictive of positive outcomes, QOL, or symptoms improvement. Conclusions Patients with severe symptoms and altered QOL at inclusion particularly benefit from GES; delay in GE is not predictive of positive outcomes. This suggests that indication for GES should be based on clinical settings rather than initial GE, and then possibly extended to patients with normal GE.
As illustrated by the Montreal classification, gastroesophageal reflux disease (GERD) is much more than heartburn and patients constitute a heterogeneous group. Understanding if links exist between ...patients' characteristics and GERD symptoms, and classify subjects based on symptom-profile could help to better understand, diagnose, and treat GERD. The aim of this study was to identify distinct classes of GERD patients according to symptom profiles, using a specific statistical tool: Latent class analysis.
An observational single-visit study was conducted in 5 European countries in 7700 adults with typical symptoms. A latent class analysis was performed to identify "latent classes" and was applied to 12 indicator symptoms.
On 7434 subjects with non-missing indicators, latent class analysis yielded 5 latent classes. Class 1 grouped the highest severity of typical GERD symptoms during day and night, more digestive and non-digestive GERD symptoms, and bad sleep quality. Class 3 represented less frequent and less severe digestive and non-digestive GERD symptoms, and better sleep quality than in class 1. In class 2, only typical GERD symptoms at night occurred. Classes 4 and 5 represented daytime and nighttime regurgitation. In class 4, heartburn was also identified and more atypical digestive symptoms. Multinomial logistic regression showed that country, age, sex, smoking, alcohol use, low-fat diet, waist circumference, recent weight gain (>5 kg), elevated triglycerides, metabolic syndrome, and medical GERD treatment had a significant effect on latent classes.
Latent class analysis classified GERD patients based on symptom profiles which related to patients' characteristics. Although further studies considering these proposed classes have to be conducted to determine the reproducibility of this classification, this new tool might contribute in better management and follow-up of patients with GERD.
Luminal serine-proteases lead to increased colonic paracellular permeability and visceral hypersensitivity in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Other proteases, ...namely cysteine-proteases (CPs), increase airway permeability by digesting epithelial tight junction proteins. In this study, we focused on constipation-predominant IBS (IBS-C) and we aimed to (i) evaluate CP levels in two cohorts of IBS patients, (ii) test if IBS-C fecal supernatant (FSN) affects permeability, and visceral sensitivity after repeated administrations in mice, and (iii) evaluate occludin expression in IBS-C colonic biopsies.
Fecal CP activity was determined using selective substrate and inhibitor (E64). The effect of papain, as positive control, and IBS-C FSN administrations were evaluated on colonic paracellular permeability and mucosal occludin levels in mice and T84 monolayers. Occludin protein levels were evaluated in IBS-C colonic biopsies. Sensitivity to colorectal distension (CRD) was measured after repeated administrations of IBS-C FSN.
We found in a subset of IBS-C patients an enhanced fecal CP activity, in comparison with healthy controls and IBS-D patients. CP activity levels positively correlated with disease severity and abdominal pain scoring. This association was confirmed by receiver operating characteristic curve analysis. In mice, repeated application of IBS-C FSN into colon triggered increased permeability, linked to the enzymatic degradation of occludin, and was associated with enhanced visceral sensitivity to CRD. Finally, occludin levels were found decreased in colonic biopsies from IBS-C patients, and IBS-C FSNs were able to degrade recombinant human occludin in vitro. All these effects were abolished by preincubation of IBS-C FSN with a CP inhibitor, E64.
These data suggest that luminal CPs may represent a new factor contributing to the genesis of symptoms in IBS.
Photodynamic therapy (PDT) is a therapeutic option in patients with a superficial esophageal cancer. Recently, PDT was shown to be effective as a salvage therapy for a local recurrence after ...chemoradiotherapy (CRT).
To compare retrospectively the results and the complications rate of PDT between consecutive patients treated in primary intent for a superficial esophageal cancer versus patients treated by PDT for a local recurrence after CRT.
Between 1999 and 2007 in a single center, 40 consecutive patients were treated by PDT for a superficial esophageal cancer, 25 (group 1) in primary intent and 15 (group 2) for a local recurrence after CRT. Two days after intravenous (IV) Photofrin (2 mg/kg), the phototherapy was performed with a dye laser. The treatment response and severe complications, defined as perforation and stricture requiring endoscopic dilation, were compared between the two groups.
The patient and tumor characteristics were not different between the two groups. In group 1, 19 out of 25 patients (76%) were successfully treated versus 8 out of 15 patients (53%) in group 2 (P= 0.17). Severe complications occurred more frequently in patients with a prior CRT (8%vs 46.7%, P= 0.008) and included two perforations and five strictures requiring endoscopic dilation, while only two strictures occurred in group 1. A prior CRT was an independent risk factor of severe complications (odds ratio OR 8.05; 95% confidence interval CI1.22-43.0).
Severe complications were significantly more frequent in patients treated after a prior CRT. PDT as a salvage therapy in patients with a local recurrence after CRT for esophageal cancer tended to be less efficient than in first-line treatment.
STUDY QUESTION
What are the types and frequency of digestive symptoms in patients with different localizations of pelvic endometriosis and which specific symptoms are related to rectal stenosis?
...SUMMARY ANSWER
There is a high prevalence of digestive complaints in women presenting with superficial pelvic endometriosis and deep endometriosis sparing the rectum.
WHAT IS KNOWN ALREADY
Women presenting with pelvic endometriosis frequently report gastrointestinal complaints of increased intensity during menstruation, which are not necessarily linked to the infiltration of the disease into the rectal wall. Even though intrarectal protrusion of the nodule can have an impact on bowel movement, only a minority of women with rectal nodules seemed to be concerned by significant narrowing of the rectum.
STUDY DESIGN AND SIZE
This three-arm cohort prospective study included 116 women and was carried out over 22 consecutive months.
PARTICIPANTS, SETTING AND METHODS
Prospective recording of data was performed for women treated for Stage 1 endometriosis involving the Douglas pouch (n = 21), deep endometriosis without digestive infiltration (n = 42) and deep endometriosis infiltrating the rectum (n = 53). Patient characteristics, pelvic pain and data from preoperative standardized questionnaires The Gastrointestinal Quality of Life Index (GIQLI), the Knowles-Eccersley-Scott-Symptom Questionnaire (KESS) and the MOS 36-Item Short-Form Health Survey (SF-36) were compared according to endometriosis localization.
MAIN RESULTS
The values of total KESS and total GIQLI score were comparable for the three groups, as were a majority of the digestive complaints. Women presenting with rectal endometriosis were more likely to report an increase in intensity and length of dysmenorrhoea, while deep dyspareunia appeared to be more severe in women with superficial endometriosis. Women presenting with rectal endometriosis were more likely to present cyclic defecation pain (67.9%), cyclic constipation (54.7%) and a significantly longer stool evacuation time, although these complaints were also frequent in the other two groups (38.1 and 33.3% in women with Stage 1 endometriosis and 42.9 and 26.2% in women with deep endometriosis without digestive involvement, respectively). No independent clinical factor was found to be related to infiltration of the rectum by deep endometriosis. Among women with rectal endometriosis, only 26.4% presented with rectal stenosis. These women were significantly more likely to report constipation, defecation pain, appetite disorders, longer evacuation time and increased stool consistency without laxatives.
LIMITATIONS
Patients treated for pelvic endometriosis in a tertiary referral centre may not be representative of the general endometriosis population presenting with those lesions. Statistically significant differences were revealed between the three groups; however, the results were based on a small number of subjects, which carries an inherent risk of type II error particularly when comparing variables with closed values.
WIDER IMPLICATIONS OF THE FINDINGS
In women presenting with pelvic endometriosis, it seems likely that various digestive symptoms are the consequence of cyclic inflammatory phenomena leading to irritation of the digestive tract, rather than to actual infiltration of the disease itself into the rectum, with the exception of a limited number of cases where the disease leads to rectal stenosis.
STUDY FUNDING/COMPETING INTEREST
The North-West Inter Regional Female Cohort for Patients with Endometriosis (CIRENDO) is financed by the G4 Group (The University Hospitals of Rouen, Lille, Amiens and Caen). No financial support was specifically received for this study. The authors declare no conflict of interest.
To compare the prevalence of anxiety and depression states and eating disorders (EDs) between patients with irritable bowel syndrome (IBS) and healthy volunteers without IBS.
IBS patients according ...to Rome III criteria referred to our tertiary care center for therapeutic management and matched volunteers without IBS were prospectively included. EDs were screened by Sick, Control, One stone, Fat, Food-French version (SCOFF-F) questionnaire. IBS symptom severity (IBS symptom severity score), stool consistency (Bristol stool scale), anxiety and depression levels (Hospital Anxiety and Depression scale), and quality of life (validated Gastrointestinal Quality of Life Index) were assessed by validated self-questionnaires.
IBS (228) patients and healthy volunteers (228) were included. Mean age was 42.5 ± 13.9 years with mainly women (76.7%). Among IBS patients, 25.4% had positive SCOFF-F compared to 21.1% of volunteers. IBS patients more frequently had a lower body mass index (BMI) than volunteers (p < 0.0001). IBS patients with ED had poorer quality of life and more stressful life events (p = 0.02) than IBS patients without ED. The prevalence of anxiety and depression was significantly higher in IBS patients with ED than in volunteers without ED, respectively (19.0% vs 1.9%, p=0.00, and 60.3% vs 19.7%, p < 0.0001).
The prevalence of ED assessed with positive SCOFF-F questionnaire was not significantly different between IBS patients and healthy volunteers. The combination of IBS and ED was associated with higher levels of anxiety or depression and poorer quality of life.
Protein metabolism contributes in the regulation of gut barrier function, which may be altered during inflammatory states. There are three major proteolytic pathways in mammalian cells: lysosomal, Ca
...2+-activated and ubiquitin–proteasome. The regulation of proteolytic activities during inflammation remains unknown in intestine. Intestinal epithelial cells, HCT-8, were stimulated by IL-1β, IFNγ and TNFα each alone or in combination (Cytomix). Proteolytic activities were assessed using fluorogenic substrates and specific inhibitors, protein expressions by Western blot. Lysosomal and Ca
2+-activated pathways were not significantly altered by any treatment. In contrast, the activity of ubiquitin–proteasome system was stimulated by IFNγ and Cytomix (155, 160 versus 100,
P
<
0.05, respectively) but remained unaffected by IL-1β and TNFα. Free ubiquitin expression, but not ubiquitinated proteins, was enhanced by IFNγ and Cytomix. The expression of proteasome 20S α1 subunit, a constitutive proteasome 20S subunit, was not altered, β5 subunit expression was weakly decreased by Cytomix and inducible β5i subunit expression was markedly increased in response to IFNγ and to Cytomix (202, 206 versus 100,
P
<
0.05, respectively). In conclusion, lysosomal, Ca
2+-activated and constitutive proteasome activities were not affected by IL-1β, IFNγ and TNFα alone or in combination, in HCT-8 cells. These results suggest that IFNγ, but not IL-1β and TNFα, increases immunoproteasome, which might contribute to enhanced antigen presentation during inflammatory bowel diseases.
An increase in intestinal gas production due to small intestinal bowel overgrowth (SIBO) is a contributing factor for flatus incontinence. The aims of our study were to assess the efficacy of ...metronidazole in a select population of patients with flatus incontinence associated with SIBO and to compare its efficacy with that of a combination of simethicone and activated charcoal (SC; Carbosylane) in randomized experimental arms.
Adult patients suffering from flatus incontinence associated with SIBO diagnosed by a glucose breath test were enrolled in the study. They were given metronidazole or Carbosylane (SC) for 10 days. The reduction in the mean daily number of gas leakages reported in a 3-day diary before and at the end of the treatment was used as the primary endpoint.
Of 52 consecutive subjects with flatus incontinence, 23 (44%) had SIBO, 16 (33%) of whom were included in and completed the study. The relative reduction in flatus incontinence episodes was significantly higher in the metronidazole than in the SC group (66.8±34.8% vs. 25±50%, P = 0.03), decreasing by more than 50% in 7 (87.5%) of the subjects in the metronidazole group compared with only 1 (12.5%) in the SC group (odds ratio 1.9, 95% confidence interval 0.9-56.9, P = 0.06).
Our results show a promising trend indicating that metronidazole might significantly improve flatus incontinence associated with SIBO and might be more successful in treating flatus incontinence than gas absorbents.