Painful or Mild-Pain Constipation? A Clinically Useful Alternative to Classification as Irritable Bowel Syndrome with Constipation Versus Functional Constipation.

PURPOSE: Abdominal pain is not used to characterize constipated patients. This study aimed to compare clinical, psychological, and physiological features in patients with IBS-constipation (IBS-C) with those in patients with functional constipation (FC) according to the intensity of abdominal pain. METHODS: All patients filled a standard Rome III questionnaire. In addition, they indicated the intensity of constipation, diarrhea, bloating, and abdominal pain on a 10-point Likert scale, and their stool form with the Bristol Stool Form Scale. Anxiety and depression were assessed with the Beck Depression Inventory and the State-Trait Anxiety Inventory. Physiological evaluation included anorectal manometry and total and segmental colonic transit time. MAIN RESULTS: A total of 546 consecutive patients, 245 with IBS-C and 301 with FC, were included. Painful constipation (PFC) was found by cluster analysis and subsequently defined as having a value over four on the Likert scale for abdominal pain. PFC was found in 67% of IBS-C patients and in 22% of FC patients. PFC patients have digestive disorders with greater frequency and report higher levels of constipation and bloating, despite similar stool form. They have higher scores of depression, state and trait anxiety, and shorter terminal transit time than mild-pain constipated patients. Compared to IBS-C patients, PFC patients report higher levels of abdominal pain (P < 0.001). Psychological and physiological parameters were similar in PFC and IBS-C patients. CONCLUSION: Painful constipation and mild-pain constipation could be an alternative way to identify constipated patients than using the diagnosis of IBS-C and FC for clinical evaluation and drug studies.

Efficacy and safety of pasireotide-LAR for the treatment of refractory bleeding due to gastrointestinal angiodysplasias: results of the ANGIOPAS multicenter phase II noncomparative prospective double-blinded randomized study.

BACKGROUND: Gastrointestinal angiodysplasias (GIADs) could be responsible for recurrent bleeding and severe anemia. Somatostatin analogs could reduce transfusion requirements in these patients but no randomized controlled study is available. The main objective of the ANGIOPAS phase II double-blinded randomized, noncomparative study was to assess the effectiveness of pasireotide-LAR in reducing transfusion requirements in patients with refractory GIADs bleeding. METHODS: A total of 22 patients with transfusion requirements ⩾6 units of packed red blood cells (pRBCs) during the 6 months prior to inclusion were randomized to receive pasireotide-LAR 60 mg (n = 10) or placebo (n = 12) every 28 days for 6 months. Patients were then followed for an additional 6 months after stopping treatment. RESULTS: The pasireotide-LAR and placebo groups were equivalent for age, sex, comorbidities and transfusion requirement during the reference period (median 13 and 9.5 pRBCs). A 50 and 83% success rate (success defined as a decrease of at least 30% of transfused pRBCs) was observed in the pasireotide-LAR arm in the Intent to Treat (ITT) and per protocol (PP) analysis respectively. The need for transfusion during the intervention period was 3 pRBC units in the pasireotide-LAR group (range 0-26) and 11.5 pRBC units in the placebo group (range 0-23). Overall, three cases with glycemic control impairment were observed in the pasireotide-LAR group including one de novo diabetes. CONCLUSION: This double-blinded noncomparative randomized phase II study suggests, for the first time, the effectiveness of pasireotide-LAR 60 mg every 28 days to decrease the transfusion requirement in patients with recurrent bleeding due to GIADs.

Sleep quality and functional gastrointestinal disorders. A psychological issue.

OBJECTIVE: Sleep disorders are often associated with functional gastrointestinal disorders (FGIDs). This study aims to evaluate the association of sleep disorders with specific FGIDs and to assess the related importance of psychological disorders. METHODS: We included 1009 consecutive patients with FGIDs (70.9% females). The patients completed a Rome III questionnaire and after a psychological evaluation on anxiety and depression they were classified according to their sleep disorders using a 7-point grading scale: Groups 1-3, drowsiness (severe, moderate, mild); Group 4, no change; Groups 5-7, insomnia (mild, moderate, severe). Multinomial logistic regression using sleep group as a dependent variable with no sleep change as reference and body mass index, FGIDs, anxiety and depression as independent variables were used for statistical analysis. RESULTS: Altogether 667 (66.1%) patients reported changes in sleep disorders, of whom 487 (48.3%) had decreased sleep and 180 (17.8%) had increased sleep while 342 (33.9%) reported no change. Depression was lower in patients with no change in sleep pattern and increased with the severity of their sleep disorder (P < 0.001). State-anxiety is associated with moderate drowsiness (P = 0.024), while trait anxiety is associated with mild insomnia (P = 0.048). FGIDs associated with sleep disorders included chest pain, epigastric pain syndrome, irritable bowel syndrome with constipation, diarrhea, bloating, fecal incontinence and proctalgia fugax. CONCLUSION: Sleep disorders are associated with FGIDs, especially in the presence of depressive symptoms.

Change of appetite in patients with functional digestive disorder. Association with psychological disorders: A cross-sectional study.

BACKGROUND AND AIMS: Changes in appetite are a frequent complaint in patients with functional gastrointestinal disorders (FGIDs). The aims of this study are to evaluate whether the changes in appetite are associated with specific FGIDs and to explore associations of these changes with symptoms of anxiety or depression. METHODS: This study included 1009 consecutive FGID patients (71% female), aged 48.9 years who all filled out a Rome III questionnaire for the evaluation of FGIDs, submitted to a psychological evaluation of symptoms of anxiety, and completed the Beck Depression Inventory questionnaire. The patients were classified according to their appetite change using a 7-point grading scale and split into three groups: those with appetite loss, those with no change in appetite, and those with increased appetite. RESULTS: Among the 1009, 496 patients (49%) reported a change in appetite, of which 332 (33%) patients reported a decrease in appetite and 164 (16%) patients reported an increase in appetite. Appetite was not affected in 51% of patients. Changes in appetite depended on gender, body mass index and psychometric evaluation scores. Increased appetite did not have specific FGIDs associations, while decreased appetite was associated with esophageal, gastroduodenal, bowel, and anorectal symptoms. The presence of depressive symptoms was also a predictor for the majority of FGIDs in decreased appetite, while anxiety trait was significant for globus and dysphagia. CONCLUSIONS: Decreased appetite was associated with FGIDs, especially in the presence of depressive symptoms. A reduced appetite would help to predict psychological disorders associated with FGIDs. FINANCIAL DISCLOSURE: None declared. LEGAL REGISTRATION: This study was a registered study in the French National Drug Agency (ANSM, Agence Nationale de Securité du Medicamentet des produits de santé, Study Number 2016-A01120-51). COMPETING INTERESTS: Michel Bouchoucha, Marinos Fysekidis, Florence Mary, Gheorghe Airinei, Cyriaque Bon, and Robert Benamouzig have no competitive interests.

Clinical, psychological, and physiological correlates of patients who defecate after meal.

BACKGROUND AND AIMS: Food is the most important synchronizer of gastrointestinal motility and secretion. Many patients with functional bowel or anorectal disorders complain of fecal urge and stool output after eating. PATIENTS AND METHODS: In this prospective observational study, 408 consecutive outpatients with functional bowel and/or anorectal disorders (74% female, 50.2±15.6 years, 24.8±5.0 kg/m²) filled Rome III questionnaires. Depression and anxiety scores, a physiological evaluation (total and segmental colonic transit time, colonic transit response to eating using a standard 1000 kcal test meal, and anorectal manometry), were measured. Univariate analysis and multivariate logistic regression were carried out according to the presence or not of stool output after eating. RESULTS: Defecation after eating was found in 21% of patients. These patients were not different according to the demographic characteristics of sex ratio (P=0.702), age (P=0.830), and BMI (P=0.314). In contrast, they had lower state anxiety (P=0.032), but similar scores of depression (P=0.240) and trait anxiety (P=0.933). They had similar manometric characteristics (anal pressure and rectal sensitivity), but a greater response to eating in all segments of the colon. There was an increase in the frequency of functional diarrhea (odds ratio=2.576, 95% confidence interval=1.312-5.056; P=0.006) and levator ani syndrome (odds ratio=2.331, 95% confidence interval=1.099-4.944; P=0.017), but no other functional bowel disorder including irritable bowel syndrome and its subtypes was found. CONCLUSION: Stool output after eating is associated with clinical disorders but not physiological parameters. This symptom is not associated with irritable bowel syndrome, but a higher frequency of functional diarrhea.

Difficult defecation in constipated patients and its relationship to colonic disorders.

BACKGROUND: The importance in constipated subjects of having difficult defecation is poorly known. According to the Rome III criteria, constipated patients are classified as having either irritable bowel syndrome with constipation or functional constipation, depending on the presence and characteristics of abdominal pain. But, the Rome III criteria also identify another group of patients, labeled as suffering from functional anorectal disorders. Within this group, two complaints are akin to being constipated, but not labeled so: having dyssynergic defecation or inadequate defecation. OBJECTIVE: The aim of this study was to search for an association between difficult defecation and colonic transit abnormalities in constipated patients and, thus, shed some light on the definition of constipation according to the Rome III criteria. PATIENTS: Four hundred four consecutive patients (81% female), aged 44.9 ± 16.6 years, with a BMI of 25.5 ± 6.4 kg/m(2) (mean ± SD), suffering from chronic constipation were included in the present study. After filling out a standard Rome III questionnaire, patients were classified as suffering from an irritable bowel syndrome with constipation or functional constipation. In addition, they were classified as complaining of difficult defecation or not. Patients completed the Bristol Stool Form Scale as well as visual analogue scales for constipation, bloating, and abdominal pain. The colonic transit time was measured using radiopaque markers and analyzed according to three sites: the right colon, the left colon, and the rectosigmoid area. RESULTS: Difficult defecation is more frequent in patients with irritable bowel syndrome with constipation (84%) than in patients with functional constipation (68%). It is associated with an increase in constipation and abdominal pain scores on Likert scales, and a longer oroanal transit time, due to a delay in the left part of the colon. CONCLUSIONS: This study demonstrates that difficult defecation is part of a more generalized colorectal dysfunction in both irritable bowel syndrome and in functional constipation patients with an overlap of symptomatology. It also demonstrates the relative inadequacy of the Rome III criteria to describe the relationship between constipation and difficult defecation.

How many segments are necessary to characterize delayed colonic transit time?

BACKGROUND AND AIMS: Measuring colonic transit time with radiopaque markers is simple, inexpensive, and very useful in constipated patients. Yet, the algorithm used to identify colonic segments is subjective, rather than founded on prior experimentation. The aim of the present study is to describe a rational way to determine the colonic partition in the measurement of colonic transit time. METHODS: Colonic transit time was measured in seven segments: ascending colon, hepatic flexure, right and left transverse colon, splenic flexure, descending colon, and rectosigmoid in 852 patients with functional bowel and anorectal disorders. An unsupervised algorithm for modeling Gaussian mixtures served to estimate the number of subgroups from this oversegmented colonic transit time. After that, we performed a k-means clustering that separated the observations into homogenous groups of patients according to their oversegmented colonic transit time. RESULTS: The Gaussian mixture followed by the k-means clustering defined 4 populations of patients: "normal and fast transit" (n = 548) and three groups of patients with delayed colonic transit time "right delay" (n = 82) in which transit is delayed in the right part of the colon, "left delay" (n = 87) with transit delayed in the left part of colon and "outlet constipation" (n = 135) for patients with transit delayed in the terminal intestine. Only 3.7 % of patients were "erroneously" classified in the 4 groups recognized by clustering. CONCLUSIONS: This unsupervised analysis of segmental colonic transit time shows that the classical division of the colon and the rectum into three segments is sufficient to characterize delayed segmental colonic transit time.

Patients with irritable bowel syndrome and constipation are more depressed than patients with functional constipation.

BACKGROUND: Psychosocial factors, such as depression, have been shown to be associated with gastrointestinal disorders like constipation. METHODS: We retrospectively compared the depression and anxiety profiles of patients with irritable bowel syndrome with constipation versus those of patients with functional constipation using validated questionnaires. Subjects rated the intensity of digestive symptoms experienced during the previous month using visual analogue scales. Colonic transit time measurements and anorectal manometry were performed. RESULTS: Of the 128 consecutive, constipated patients included (84% females, mean age 49.7 ± 15.5 years) 66 suffered from irritable bowel syndrome with constipation and 62 from functional constipation. Demographic and physiological traits were similar in the two groups. Patients suffering from irritable bowel syndrome with constipation reported higher depression scores (18.8 ± 1.4 vs 12.7 ± 1.3, P=0.002) and higher symptom intensity scores for constipation (6.2 ± 0.3 vs 4.3 ± 0.4, P<0.001), bloating (6.7 ± 0.3 vs 3.3 ± 0.4, P<0.001) and abdominal pain (6.0 ± 0.3 vs 2.7 ± 0.4, P<0.001) than patients with functional constipation. Multiple linear regression showed positive correlations between symptom intensity and depression and anxiety scores for functionally constipated patients only. CONCLUSIONS: Our results support the integration of a psychosocial component to the traditional treatment of constipated patients; however, further research exploring causality between psychosocial factors and specific gastrointestinal disorders would contribute to developing a tailored therapeutic approach.

Anxiety and depression as markers of multiplicity of sites of functional gastrointestinal disorders: a gender issue?

BACKGROUND: Anxiety and depression are frequently present in patients with different types of functional gastrointestinal disorders (FGID), and seem to play a major part in both the perception of symptoms and the outcome of treatment. AIMS: The aim of the present study was therefore to evaluate levels of anxiety and depression in adult patients according to the extent and the type of FGID. METHODS: Three hundred and eighty-five consecutive patients (72% female) were evaluated. Each patient filled a standard clinical questionnaire based on diagnostic questions for uro-genital complaints and for FGID according to the Rome III criteria. In addition, they indicated on a 10-cm visual analog scale (VAS) the intensity of constipation, diarrhea, bloating, and abdominal pain, and stool description using the Bristol Stool Form Scale. Anxiety and depression were evaluated using Beck Depression Inventory and Anxiety State and Trait Anxiety Inventory. RESULTS: In FGID patients, levels of depression, state and trait anxiety are higher in patients with several sites of complaint. Females are more depressed than males, regardless of the level of FGID. Females tend to react emotionally to stress with a lot of anxiety ("state" anxiety), as well as in the long run ("trait" anxiety). VAS parameters for constipation, bloating and abdominal pain were related to psychological scores in contrast to VAS diarrhea and stool form. In males, the extent of sites of FGID was strongly related to trait anxiety. In females, it was strongly related to depression. CONCLUSION: Different types of FGID are associated with depression and anxiety according to the number of sites of complaints linked to gender and psychological parameters, as well as the magnitude of complaint expressed by the VAS.

Postprandial protein metabolism but not a fecal test reveals protein malabsorption in patients with pancreatic exocrine insufficiency.

BACKGROUND & AIMS: Pancreatic exocrine insufficiency (PEI) impairs fat absorption, but few data are available on protein absorption. We investigated this question in patients with chronic pancreatitis, both in the absence and presence of enzyme therapy, using a stable isotope sensitive method. METHODS: Eleven patients with sustained PEI and regular enzyme substitution were investigated at hospital, after a washout period without enzyme substitution, and later after reintroduction of substitution. The digestibility and postprandial metabolism of dietary protein were characterized after the ingestion of a semi-synthetic single meal containing 20 g (15)N-labeled casein. RESULTS: At baseline, 20 ± 8% of dietary nitrogen was transferred to the metabolic pools vs. 24.5 ± 7% under enzyme treatment (P = 0.04). After treatment, the transfer of dietary nitrogen tended to increase in plasma amino acids, and increased significantly in plasma proteins and the deamination pool. In contrast, the fecal excretion of dietary nitrogen did not demonstrate any treatment effect. In patients not receiving insulin for diabetes, the treatment stimulated insulin secretion. CONCLUSIONS: Protein malabsorption was mostly undetectable using standard fecal tests. The study of the postprandial fate of dietary protein revealed a moderate increase of its transfer to metabolic pools after enzyme substitution.

Is the colonic response to food different in IBS in contrast to simple constipation or diarrhea without abdominal pain?

BACKGROUND: Colonic response to food (CRF) is abnormal in irritable bowel syndrome (IBS) patients. AIMS: The aim of this study was to compare CRF in patients who complain of abnormal defecation pattern according to the presence or absence of abdominal pain. METHODS: One hundred forty-nine patients and 50 controls were studied: 96 IBS patients (46 IBS-C, 13 IBS-D, 15 IBS-M, and 22 IBS-U not included), 43 patients with functional constipation (group C) and ten with functional diarrhea (group D). Clinical evaluation and visual analog scales about four items (constipation, diarrhea, abdominal bloating and abdominal pain) were filled by all subjects. Colonic transit time (CTT) was measured in fasting conditions and after eating a standard 1,000-cal test meal. CRF was quantified by calculating the variation in number of markers between the two films. RESULTS: The frequency of meal-related symptoms did not vary among the different groups of patients but was significantly higher than in controls. Compared to IBS-C patients, constipated patients of the group C had longer total and segmental colonic transit time, and compared to IBS-D patients, diarrheic patients of the group D had shorter oro-anal and segmental colonic transit time except in the recto-sigmoid area. CRF was different in patients and controls, and differed between IBS and non IBS patients with similar transit abnormalities. Stool output was greater in patients of the group D than in patients of the IBS-D group. CONCLUSION: The different subgroups of IBS patients have different CRF patterns, distinct from subjects with constipation and diarrhea, but without abdominal pain.

Ultra high temperature treatment, but not pasteurization, affects the postprandial kinetics of milk proteins in humans.

Although the chemical and physical modifications to milk proteins induced by technological treatments have been characterized extensively, their nutritional consequences have rarely been assessed in humans. We measured the effect of 2 technological treatments on the postprandial utilization of milk nitrogen (N), pasteurization (PAST) and ultra high temperature (UHT), compared with microfiltration (MF), using a sensitive method based on the use of milk proteins intrinsically labeled with (15)N. Twenty-five subjects were studied after a 1-wk standardization of their diet. On the day of the investigation, they ingested a single test meal corresponding to 500 mL of either MF, PAST, or UHT defatted milk. Serum amino acid (AA) levels as well as the transfer of (15)N into serum protein and AA, body urea, and urinary urea were determined throughout the 8-h postprandial period. The kinetics of dietary N transfer to serum AA, proteins, and urea did not differ between the MF and PAST groups. The transfer of dietary N to serum AA and protein and to body urea was significantly higher in UHT than in either the PAST or MF group. Postprandial deamination losses from dietary AA represented 25.9 +/- 3.3% of ingested N in the UHT group, 18.5 +/- 3.0% in the MF group, and 18.6 +/- 3.7% in the PAST group (P < 0.0001). The higher anabolic use of dietary N in plasma proteins after UHT ingestion strongly suggests that these differences are due to modifications to digestive kinetics and the further metabolism of dietary proteins subsequent to this particular treatment of milk.

Expression of ghrelin in fundus is increased after gastric banding in morbidly obese patients.

BACKGROUND: Ghrelin, a 28 amino-acid acylated orexigenic peptide secreted by the stomach, acts on the hypothalamic arcuate nucleus which stimulates feeding behavior. Serum ghrelin level increases during fasting and decreases after a meal. Serum ghrelin is low in obese patients.Whether ghrelin is implicated in weight loss in obese patients after laparoscopic adjustable gastric banding (LAGB) is still debated. In this study, we assessed serum ghrelin level and gastric fundus expression before and 1 year after LAGB. METHODS: Gastric fundus expression of ghrelin was assessed by immunohistochemistry using a rabbit anti-human ghrelin antibody simultaneously with serum total ghrelin levels (RIA) in 13 obese patients (2 men and 11 women) after an overnight fast, before LAGB and 1 year after. Immunostaining was "blindly" analyzed by a single pathologist, measuring the density of stained fundic cells near muscularis mucosa. RESULTS: Mean age of the 13 patients was 41 years, and mean baseline BMI was 46 kg/m2. Pre- and post-LAGB gastric expression of ghrelin was analyzable in 11 patients. It was always identified, mostly with moderate or intense staining. Mean density of stained cells significantly increased 1 year after LAGB: 31/mm2 (21-38) before vs 38/mm2 (27-57) after surgery (P<0.01). This increase did not correlate with changes in BMI, nor did pre- or postoperative gastric expression of ghrelin correlate with the corresponding serum values. CONCLUSION: We showed for the first time that ghrelin expression assessed by immunohistochemistry was present in the fundus of all 11 obese patients and that it was significantly increased 1 year after LAGB, which would exclude a pathogenetic role of ghrelin in weight loss after LAGB.