Biopsychosocial Model and Perceived Constipation Severity According to the Constipation Phenotype.

PURPOSE: Constipation is a frequent complaint of patients with functional bowel disorders. The present study aimed to evaluate the relationship between the perceived constipation severity with demographics, clinical, physiological, and psychological parameters in constipated patients. PATIENTS AND METHODS: Four hundred seven constipated patients were included and had clinical, physiological, and psychological evaluation. The self-reported severity of constipation was analyzed using stepwise linear regression in the total population and within each clinical group. RESULTS: The patients were mainly of female gender (81%) and were 47.4 ± 16.5 years old. They complained of IBS (65%), and 62% had defecation disorders. The depression scale was abnormal in 200 patients (49%). The relationships of the constipation severity varied according to the Rome IV phenotype. In all phenotypes, it was positively associated with bloating severity, and negatively with Bristol stool form. In IBS patients, perceived constipation severity was also associated with abdominal pain severity. CONCLUSION: Our data support the hypothesis that perceived constipation severity is associated with clinical and physiological factors but not demographics and psychological factors. Besides, the relationships of perceived constipation severity with these factors vary according to clinical phenotypes.

Clinical and psychological correlates of soiling in adult patients with functional gastrointestinal disorders.

BACKGROUND/AIMS: Fecal soiling (FS) is the staining of underwear without loss of significant amounts of fecal material. It is frequently associated with defecation disorders in children. The aim of this study was to search for psychological and clinical correlates of adult patients with soiling. Clinically, the complaint of staining is confused with that of fecal incontinence (FI) in the mind of both patients and attending physicians. DESIGN: Observational study PATIENTS AND METHOD: We included 1454 consecutive outpatients (71% females). They filled out the Rome III questionnaire for functional gastrointestinal disorders (FGIDs); Beck depression inventory, and state and trait anxiety questionnaires; and Likert scales for constipation, diarrhea, bloating, and abdominal pain. Data were analyzed using ANOVA and logistic regression analysis. RESULTS: Soiling was found in 123 patients (8.5%). They reported similar frequencies of esophageal, gastroduodenal, and abdominal pain as patients without soiling. In contrast, patients with soiling reported higher prevalence of IBS, such as IBS-Diarrhea, Mixed-IBS, functional diarrhea, functional constipation, and levator ani syndrome, and higher Likert scale for diarrhea, bloating, abdominal pain, and softer stools. The multivariable logistic regression analysis shows that patients with soiling have increased odds to report IBS (P = 0.019; OR = 1.958; 95% CI = [1.118-3.431]), functional diarrhea (P = 0.040; OR = 1.901; 95% CI = [1.028-3.513]), and high Diarrhea Likert scale (P < 0.001; OR = 1.215; 95% CI = [1.130-1.306]). No association was found with psychological evaluation. CONCLUSION: In FGID patients, soiling is not associated with psychological disorders and is mainly associated with IBS and functional diarrhea.

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.

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.

Severe colitis in patients with melanoma treated with BRAF/MEK inhibitors.

BACKGROUND AND AIMS: Dual blockade of BRAF and MEK kinases is a standard of care for metastatic V600E/K BRAF mutant melanoma. This study reports the first systematic description of colitis due to BRAF and MEK inhibitors. METHODS: We studied consecutive patients with melanoma, treated with BRAF and MEK inhibitors, who had colitis requiring hospitalisation. Electronic files were studied; endoscopic biopsies and colectomy specimens were read centrally. RESULTS: Between January 2021 and March 2022, nine women and one man, aged 50-90 years, were studied. Nine patients received encorafenib and binimetinib; one patient received dabrafenib and trametinib. The main symptoms were diarrhoea, haematochezia, abdominal pain and intestinal obstruction. Blood tests showed anaemia, increased CRP and low serum albumin levels in most patients. All patients had ulcerations of the right colon with (2/10) or without (8/10) stenosis of the ileocecal valve, and 4/10 patients also had ulcerations distal to the right colon. Histopathological findings were suggestive of ischaemia and mild inflammation. Nine of the 10 patients discontinued BRAF/MEK inhibitors. Drugs were reintroduced in four patients, three of whom had a severe relapse of diarrhoea. Two patients required surgery and underwent intestinal resection. One patient died of enterocolitis. CONCLUSION: BRAF/MEK inhibitors can induce severe colitis characterised by ulcerations of the right colon.

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.

COLIGENTA treatment of small intestinal bacterial overgrowth. Results of an open study.

PURPOSE: The treatment of small intestinal overgrowth (SIBO) varies according to the center. The present study aimed to evaluate the efficacy of COLIGENTA, an association of colimycin and gentamycin, on SIBO symptomatology and breath test normalization PATIENTS AND METHODS: In this prospective cross-sectional open study, 150 patients with functional bowel disorders and SIBO diagnosed by lactulose hydrogen breath test (LHBT) underwent COLIGENTA oral treatment. A new HLBT was performed 4 weeks after the first HLBT. RESULTS: The patients were mainly female (74%), with a mean age of 47.4 ±â€¯16.2 years and a body mass index of 26.2 ±â€¯5.9 kg/m². After treatment, a decrease of expired hydrogen concentration (P<0.001) was found in the entire population. Improvement of gastrointestinal symptoms was found in 129 patients (86%), while the breath test's normalization was found in 62 patients (42%). Logistic regression showed that normalization of bowel symptoms was not associated with demographics, clinical, or hydrogen breath concentration. In contrast, normalization of LHBT was associated with an increase of breath hydrogen concentration at time 100 min during the first test (P = 0.003; OR=1.072; 95%CI= [1.023-1.123]). CONCLUSION: The present study shows that 10-days of COLIGENTA treatment has a high SIBO clinical improvement rate and can be used as the first or second treatment line.

Clinical, Physiological, and Psychological Correlates of the Improvement of Defecation during Menses in Women with Functional Gastrointestinal Disorders.

BACKGROUND/AIMS: Little is known about the improvement in defecation frequently reported by women around menses. We aimed to describe clinical, physiological, and psychological correlates of this improvement in those with functional bowel disorders. PATIENTS AND METHODS: We recruited 478 consecutive premenopausal adult females with no indication of gynecologic or psychiatric disease, who were attending an outpatient functional bowel disorders clinic. Patients completed a Rome III questionnaire, psychological evaluation stool form, and a 10-point Likert scale for constipation, diarrhea, bloating, and abdominal pain. These patients underwent physiological tests, anorectal manometry, and colonic transit time and were classified according to the presence or the absence of improvement in defecation during menses. The reverse selection procedure was used for model selection during multivariate logistic regression where statistically significant variables (p < 0.01) remained in the adjusted model. RESULTS: Ninety-seven patients (20%) reported easier defecation during menstruation. These patients were younger (p < 0.001) but had similar body mass indices and psychological profiles as the other patients. Clinically, they only reported more frequent irritable bowel syndrome (IBS) with constipation (p = 0.007), with harder stools (p = 0.005) and delayed left colon transit time (p = 0.002). No anorectal manometric parameter was different between the 2 groups. CONCLUSION: Improvement of constipation during menses is mainly associated with younger age and constipation-IBS phenotype and not with functional constipation.

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.

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.

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.

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.