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1.
Cytopathology ; 24(3): 177-84, 2013 Jun.
Article in English | MEDLINE | ID: mdl-21917031

ABSTRACT

OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a routine technique to assess solid pancreatic lesions. The aim of this study was to analyse the effect of optimizing laboratory procedures for specimen preparation on the rate and accuracy of the procedure. METHODS: All EUS-FNAs of solid pancreatic lesions performed during the year 2000 (Period 1) and from May 2003 to May 2004 (Period 2) were analysed. During Period 1, one experienced gastroenterologist performed all EUS-FNAs, making direct smears and retrieving small fragments if present on the smear for histology. In Period 2, two endoscopists performed the EUS-FNAs and all the material was emptied into a vial containing a fixative. Slide preparation was carried out in the pathology laboratory: one slide was processed using cytocentrifugation and cell blocks were made from left-over material. Neither period utilized rapid on-site evaluation. RESULTS: During the two periods, 67 and 102 FNAs were analysed and showed significantly different (P < 0.001) non-diagnostic rates of 22.8% and 4.2%, respectively. The increased diagnostic yield can be explained by the modified laboratory procedures and to a lesser extent by the increased experience of the gastroenterologists. Sensitivity, specificity, PPV, NPV and accuracy in the second time period were, respectively, 90.6%, 100%, 100%, 81.8% and 93.4%, not significantly different from the first time period. CONCLUSION: This study shows that accurate EUS-FNA results may be obtained with a low non-diagnostic rate comparable to those reported for rapid on-site evaluation by optimizing laboratory specimen processing in a setting of solid pancreatic lesions.


Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Pancreatic Neoplasms/diagnosis , Specimen Handling , Cytodiagnosis , Follow-Up Studies , Humans , Pancreatic Neoplasms/classification , Pancreatic Neoplasms/pathology
2.
Acta Gastroenterol Belg ; 86(2): 288-297, 2023.
Article in English | MEDLINE | ID: mdl-37428161

ABSTRACT

Background and aims: Irritable Bowel Syndrome (IBS)-like symptoms are frequent following bariatric surgery. This study aims to evaluate the frequency of IBS symptoms severity before and after bariatric surgery and their association with short-chain fermentable carbohydrates (FODMAPs) consumption. Patients and methods: IBS symptoms severity in a cohort of obese patients was evaluated prospectively before, 6 and 12 months after bariatric surgery by validated questionnaires and tools (Irritable Bowel Syndrome Severity Scoring System (IBS SSS), Bristol Stool Scale (BSS), Quality of Life Short- Form-12 (SF-12), Hospital Anxiety and Depression scale (HAD)). FODMAPs consumption and its association with IBS symptom severity was evaluated by using a food frequency questionnaire focused on high-FODMAPs food consumption. Results: Fifty-one patients were included (41 female; mean age 41 years (SD: 12)), 84% received a sleeve gastrectomy, and 16% a Roux-en-Y gastric bypass. Symptoms compatible with IBS were observed in 43% of patients before surgery, in 58% of patients at 6 months and 33% at 12 months (NS, p-value=0,197 and 0,414). In a multivariate model, a significant association was found between the IBS SSS score and lactose consumption at 6 months (ß = + 58, 1; p = 0.03), and with polyols consumption at 12 months (ß = + 112,6; p = 0.01). Conclusions: Mild to moderate IBS symptoms are frequent in obese patients before bariatric surgery. A significant association between lactose and polyols consumption and IBS SSS score was observed after bariatric surgery, suggesting a potential link between the severity of IBS symptoms and some specific FODMAPs consumption.


Subject(s)
Bariatric Surgery , Irritable Bowel Syndrome , Humans , Female , Adult , Irritable Bowel Syndrome/epidemiology , Irritable Bowel Syndrome/etiology , Disaccharides , Lactose , Prospective Studies , Quality of Life , Monosaccharides , Bariatric Surgery/adverse effects , Obesity/epidemiology , Obesity/surgery
3.
Acta Gastroenterol Belg ; 85(2): 311-319, 2022.
Article in English | MEDLINE | ID: mdl-35709775

ABSTRACT

Background and study aims: The role of malnutrition on the prognosis of hospitalized cirrhotic patients is incompletely studied. Our aim was to determine the prevalence of malnutrition, functional scores and their impact on prognosis of hospitalized cirrhotic patients. Patients and methods: This retrospective study included all patients with cirrhosis hospitalized in the gastroenterology unit at Saint-Luc university hospital, Brussels between April 2014 and September 2014. Nutritional status was evaluated according to minimum clinical summary diagnostic criteria. Cirrhosis-related complications or death occurrence were analysed in a one-year follow-up. Results: 95 cirrhotic patients were assessed for nutritional status and outcomes. Malnutrition affected 45.3% of patients and was more frequent with the severity of cirrhosis: 29% in Child-Pugh A, 48.8% in Child-Pugh B and 72.2% in Child-Pugh C patients. 58.9% of patients developed cirrhosis-related complications (60.7% in the malnutrition group vs. 39.3%, p<0.001, OR 5.06, IC95 1.90-14.58) and 33.7% of patients died (68.75% vs. 31.25%, p=0.002, OR 4.33, IC95 1.62-12.28). Adjusting for age, sodium, MELD, Charlson index, hepatocellular carcinoma, platelets, diabetes, prognostic nutritional index and Braden scale, malnutrition was significantly associated with higher mortality and morbidity rates with an OR of 3.56 (CI95 1.55-8.16) and 2.09 (CI95 1.16-3.77) respectively. Braden scale was significantly associated with higher mortality (p=0.027, OR 1.25, CI95 1.03-1.52) whereas prognostic nutritional index was associated with higher morbidity (p=0.001, OR 0.94, CI95 0.90-0.98). Conclusion: Malnutrition is highly prevalent in hospitalized cirrhotic patients. Malnutrition, low prognostic nutritional index and low Braden scale are associated with poor outcomes in cirrhosis.


Subject(s)
Malnutrition , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Malnutrition/diagnosis , Malnutrition/epidemiology , Malnutrition/etiology , Nutrition Assessment , Nutritional Status , Prognosis , Retrospective Studies , Severity of Illness Index
4.
Acta Gastroenterol Belg ; 85(3): 499-504, 2022.
Article in English | MEDLINE | ID: mdl-35770285

ABSTRACT

Background and study aims: Gastrointestinal endoscopic procedures have evolved significantly in the last sixty years revolutionising the approach to the diagnostic and therapeutic spheres of medicine. Despite the advantages of using natural orifices to the bowel, adverse events (AE) may occur following endoscopy. Systematic AE registration is an objective in every realm of quality medicine. Despite the obvious advantage as a quality indicator, tracking endoscopy-related AE is not evident. The current study aimed at tracking all AE of all endoscopic procedures during a 3-month period. The three methods used were voluntary reporting by the endoscopist and by the patient in parallel with retrospective data analysis of patients' electronic medical records to allow capture of all AE and comparison of the three methods. Patients and methods: During a 3-month period endoscopists and patients were requested to report any possible AE. At the end of the period, a systematic review of all patient files was performed to track all AE related to the endoscopic procedure or the endoscopyrelated anaesthesia. In total 2668 endoscopic procedures were reviewed. Results: The total AE rate was 1.95%. Only half (51.9%) of all AE were voluntarily reported by endoscopists, the other half were extracted from the electronic medical record. There were no patient-reported AE. Although the majority (66.7%) of unreported AE were mild, these findings illustrate that voluntary AE reporting is unreliable. However, the retrospective tracking process proved to be difficult and time-consuming. Conclusions: The current study highlighted that systematic registration of all endoscopy-related AE is feasible, but challenging because of multiple hurdles. More practical methods are warranted to obtain reliable and long-term data as part of endoscopy quality measures.


Subject(s)
Endoscopy, Gastrointestinal , Endoscopy, Gastrointestinal/adverse effects , Humans , Retrospective Studies
5.
Acta Gastroenterol Belg ; 85(2): 360-382, 2022.
Article in English | MEDLINE | ID: mdl-35709780

ABSTRACT

BACKGROUND: Irritable bowel syndrome (IBS) is characterised by recurrent abdominal pain related to defaecation or associated with altered stool frequency or consistency. Despite its prevalence, major uncertainties in the diagnostic and therapeutic management persist in clinical practice. METHODS: A Delphi consensus was conducted by 20 experts from Belgium, and consisted of literature review and voting process on 78 statements. Grading of recommendations, assessment, development and evaluation criteria were applied to evaluate the quality of evidence. Consensus was defined as > 80 % agreement. RESULTS: Consensus was reached for 50 statements. The Belgian consensus agreed as to the multifactorial aetiology of IBS. According to the consensus abdominal discomfort also represents a cardinal symptom, while bloating and abdominal distension often coexist. IBS needs subtyping based on stool pattern. The importance of a positive diagnosis, relying on history and clinical examination is underlined, while additional testing should remain limited, except when alarm features are present. Explanation of IBS represents a crucial part of patient management. Lifestyle modification, spasmolytics and water-solube fibres are considered first-line agents. The low FODMAP diet, selected probiotics, cognitive behavioural therapy and specific treatments targeting diarrhoea and constipation are considered appropriate. There is a consensus to restrict faecal microbiota transplantation and gluten-free diet, while other treatments are strongly discouraged. CONCLUSIONS: A panel of Belgian gastroenterologists summarised the current evidence on the aetiology, symptoms, diagnosis and treatment of IBS with attention for the specificities of the Belgian healthcare system.


Subject(s)
Irritable Bowel Syndrome , Humans , Belgium/epidemiology , Consensus , Constipation/drug therapy , Diarrhea , Irritable Bowel Syndrome/diagnosis , Irritable Bowel Syndrome/epidemiology , Irritable Bowel Syndrome/etiology
8.
Ann Oncol ; 20(8): 1375-82, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19465422

ABSTRACT

BACKGROUND: Early radiological tumor shrinkage may be associated with better long-term outcome in chemorefractory metastatic colorectal cancer (cmCRC) treated with cetuximab. We aimed at validating this in a large and independent series. PATIENTS AND METHODS: Of the 329 patients, 289 had a measurement both at baseline and week 6. Tumor shrinkage was expressed as a relative decrease compared with baseline and categorized according to a previously reported cut-off value ( approximately 10%) or used as a continuous variable. RESULTS: Median time to progression (TTP) was 6.1 [95% confidence interval (CI) 5.1-7.2] versus 1.5 months (95% CI 1.4-1.7) in patients with [99 patients (34.3%)] or without [190 patients (65.7%)] tumor shrinkage, respectively, at week 6 [hazard ratio (HR) 0.23 (95% CI 0.17-0.32)]. The median overall survival (OS) was 13.7 (CI NA) versus 6.9 months (95% CI 6.1-7.7) [HR 0.21 (95% CI 0.14-0.32)], respectively. In a multivariate model, early tumor decrease outperformed skin toxicity as a predictor of long-term outcome. CONCLUSIONS: Tumor shrinkage at 6 weeks is a strong predictor of TTP and OS in cmCRC patients treated with cetuximab with or without irinotecan. This suggests early tumor shrinkage is the hallmark of efficacy of cetuximab and reliably identifies the subpopulation that is sensitive to the drug. Early tumor shrinkage can be used as a marker of efficacy in clinical practice, as such or in combination.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/drug therapy , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Cetuximab , Colorectal Neoplasms/pathology , Disease-Free Survival , Humans , Irinotecan , Multivariate Analysis , Radiography , Regression Analysis , Treatment Outcome
9.
Acta Gastroenterol Belg ; 82(2): 257-260, 2019.
Article in English | MEDLINE | ID: mdl-31314185

ABSTRACT

It has recently been shown that duodenal foveolar gastric metaplasia (FGM) sometimes presents as a polyp. The mechanism by which FGM develops into a polypoid lesion is unknown and it is unclear whether this form of FGM is indistinguishable from other polypoid lesions or whether endoscopists do not recognize it because they are unfamiliar with it. We identified and retrieved archival cases of FGM endoscopically suspicious for adenomatous polyp and examined their pathological, clinical and endoscopic features. Endoscopic features of the 13 identified FGMs presenting as polyps were heterogeneous and overlapping with those of adenomatous polyps. FGM was frequently associated with mucosal and submucosal Brunner's glands, but defining and recognizing hyperplasia of these glands remains difficult. Other pathological features could not explain the development of a polypoid lesion. The endoscopic features of FGM polyps are non-specific, overlapping with those of adenomatous polyps. FGM polyps probably acquire their polypoid aspect due to association with Brunner's gland hyperplasia (BGH), which also arises due to chronic inflammation and damage. Because BGH is ill-defined and difficult to recognize, while FGM is diagnosed easily, this type of polypoid lesions has until now only been recognized based on the presence of FGM, although FGM is most likely a secondary phenomenon and not the primary cause of the polyp.


Subject(s)
Brunner Glands/diagnostic imaging , Duodenal Ulcer/pathology , Endoscopy, Digestive System , Hamartoma/pathology , Intestinal Polyps , Metaplasia , Brunner Glands/pathology , Duodenal Diseases/diagnostic imaging , Duodenal Diseases/pathology , Hamartoma/diagnostic imaging , Humans , Intestinal Polyps/diagnostic imaging , Intestinal Polyps/pathology , Metaplasia/diagnostic imaging , Metaplasia/pathology
10.
United European Gastroenterol J ; 7(2): 307-315, 2019 03.
Article in English | MEDLINE | ID: mdl-31080615

ABSTRACT

Background and aims: The symptom-based diagnostic criteria for irritable bowel syndrome (IBS) have recently been revised in the Rome IV consensus. On the other hand, with rising public awareness of IBS, self-diagnosis and self-management is also increasing. We compared the prevalence and impact of Rome IV-based IBS vs self-diagnosed IBS in the general population. Methods: An internet panel filled out an online survey on bowel symptoms and their impact on health care utilization and daily activities. Results: A representative internet panel of 1012 individuals completed the online survey. Bowel symptoms were present in 68.6% of the population. Of these, 21% consulted a physician for these symptoms in the last year and 42% earlier. Rome IV IBS criteria were fulfilled by 5.5%, and these were younger and more likely to be female. In this subset, 37% had consulted a physician for IBS symptoms in the preceding year and 29% had done so earlier. A colonoscopy had been performed in 22%. Based on a brief description, 17.6% of the population self-identified as suffering from IBS (p < 0.001 compared to Rome IV IBS prevalence), and these were more likely to be female. Concordance with the Rome IV criteria was only 25%, but except for a lower reporting of pain, the symptom pattern, severity, impact on daily life, inability to work and health care utilization were similar to the Rome IV group. A total of 134 days of absence from work were attributed to bowel symptoms in those self-reporting with IBS. Conclusion: In the general population, bowel symptoms are highly prevalent, and the self-reported "IBS" is three times more prevalent than according to Rome IV criteria. Self-reported IBS is associated with a similar impact on health care utilization and quality of life but a higher impact on absence from work.


Subject(s)
Irritable Bowel Syndrome/epidemiology , Adult , Aged , Female , Humans , Irritable Bowel Syndrome/diagnosis , Male , Middle Aged , Patient Acceptance of Health Care , Population Surveillance , Prevalence , Referral and Consultation , Self Report , Symptom Assessment , Young Adult
11.
Ann Oncol ; 19(3): 508-15, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17998284

ABSTRACT

BACKGROUND: KRAS mutation status is a candidate marker for predicting survival in patients with metastatic colorectal cancer (mCRC) treated with cetuximab (CTX). PATIENTS AND METHODS: We studied the KRAS mutation status of 113 patients with irinotecan refractory mCRC treated with CTX in clinical trials. A predictive model for objective response (OR), progression-free survival (PFS) and overall survival (OS) was constructed using logistic and Cox regression. RESULTS: OR was seen in 27 of 66 KRAS wild-type (WT) patients versus 0 of 42 in KRAS mutants. Median OS was significantly better in KRAS WT versus mutants (43.0 versus 27.3 weeks; P = 0.020). Decrease in tumor sizes was significantly larger at all time points in WT patients. KRAS WT patients with an initial relative decrease of tumor size >9.66% at week 6 had a significantly better median OS compared with all other patients (74.9 versus 30.6 weeks; P = 0.0000025). Within KRAS WT patients OS was significantly better in patients with an initial decrease compared with those without [median OS: 74.9 versus 30.6 weeks (P = 0.00000012)]. CONCLUSIONS: KRAS WT status is associated to survival benefit in CTX treated mCRC. This benefit is even more pronounced in those patients with early radiological response. These characteristics may be exploited for response prediction.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Mutation , Proto-Oncogene Proteins/analysis , ras Proteins/analysis , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Cetuximab , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/mortality , Disease-Free Survival , Female , Humans , Irinotecan , Logistic Models , Male , Middle Aged , Proportional Hazards Models , Proto-Oncogene Proteins p21(ras) , Retrospective Studies , Sensitivity and Specificity , Survival Rate , Tomography, X-Ray Computed
12.
Endoscopy ; 40(11): 892-8, 2008 Nov.
Article in English | MEDLINE | ID: mdl-19009481

ABSTRACT

BACKGROUND AND STUDY AIMS: The aim of this retrospective study was to assess safety and efficacy of stepwise radical endoscopic resection (SRER) in patients with Barrett's esophagus with high-grade intraepithelial neoplasia (HGIN) or early cancer. PATIENTS AND METHODS: Patients undergoing SRER between 2000 and 2006 were retrospectively evaluated. Patients with Barrett's esophagus who also had HGIN or early cancer were included if they had no signs of submucosal infiltration or metastases. SRER was performed using the cap-technique, at 8-week intervals until all Barrett's esophagus was removed. Follow-up endoscopy was scheduled every 6 months. RESULTS: A total of 34 patients were included (31 male, mean 67 years, median Barrett's dimensions C1M4). HGIN / early cancer was eradicated in all patients in a median of two endoscopic resection sessions (IQR 1-2 sessions). Twelve patients underwent additional argon plasma coagulation for small islets or an irregular Z-line. Barrett's esophagus was eradicated in 28 patients (82 %). Complications occurred in 3/34 patients (9 %): two perforations, one delayed bleeding. In all, 19 patients (56 %) developed dysphagia, which was resolved with dilatation or stent placement. During a median follow-up period of 23 months (IQR 15 - 41 months), HGIN / early cancer recurred in three patients (9 %): two were retreated with endoscopic resection and one patient was referred for curative surgery. Five patients (15 %) had recurrence of nondysplastic Barrett's esophagus. At the end of the follow-up period all patients were free of HGIN / early cancer (one patient after surgery), and 23 patients (68 %) had complete endoscopic and histological eradication of Barrett's esophagus. CONCLUSIONS: SRER resulted in complete eradication of HGIN/early cancer in all patients, and eradication of Barrett's esophagus in a majority of cases. A significant number of patients develop dysphagia, which can be successfully treated endoscopically.


Subject(s)
Barrett Esophagus/pathology , Barrett Esophagus/surgery , Carcinoma in Situ/surgery , Endoscopy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Aged , Carcinoma in Situ/pathology , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
13.
Acta Gastroenterol Belg ; 80(4): 493-497, 2017.
Article in English | MEDLINE | ID: mdl-29560645

ABSTRACT

Endoscopic retrograde cholangiopancreatography (ERCP) in Billroth II patients is challenging and different endoscopes can be used. We retrospectively analysed 67 ERCP procedures in 38 Billroth II patients focussing on endoscope type and respective technical success and adverse event rate. 33 (49.2 %) ERCPs were performed using a duodenoscope, 87.9 % were successful and 3 were completed with the single-balloon enteroscope. 28 (41.8 %) ERCPs were performed with the single-balloon enteroscope, 82.1 % were successful and 2 were completed with a paediatric colonoscope. For 6 (9.0 %) ERCPs a paediatric colonoscope was used but only 3 (50.0 %) were successful. Overall technical success rate was 82.1 % without difference between the success rate of the duodenoscope and the single-balloon enteroscope. Overall adverse event rate was 10.5 %: 6.1 % duodenoscope,10.7 % single-balloon enteroscope, 33.3 % paediatric colonoscope. The duodenoscope allowed all conventional ERCP procedures, whereas the singleballoon enteroscope required dedicated ERCP catheters and did not allow metallic stent placement. However, the single-balloon enteroscope facilitated access to the papilla and sphincteroplasty allowed direct cholangioscopy. ERCP indications were bile duct stones (53.7 %), cholangitis (20.9 %), chronic pancreatitis (20.9 %), pancreatic cancer (1.5 %) and liver transplantation (3%). Therapeutic ERCP success rate is high in patients with Billroth II gastrectomy using either a conventional duodenoscope or the single-balloon enteroscope, with an acceptable and comparable adverse event rate. The choice of endoscope may depend on local experience, post-operative anatomy and therapeutic indication.


Subject(s)
Balloon Enteroscopy , Cholangiopancreatography, Endoscopic Retrograde/instrumentation , Duodenoscopes , Gastrectomy/methods , Gastroenterostomy , Aged , Aged, 80 and over , Balloon Enteroscopy/adverse effects , Belgium , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Duodenoscopes/adverse effects , Female , Fluoroscopy , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Treatment Outcome
14.
Aliment Pharmacol Ther ; 46(11-12): 1103-1111, 2017 12.
Article in English | MEDLINE | ID: mdl-28983926

ABSTRACT

BACKGROUND: The Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire is frequently used in clinical trials of constipation. However, the threshold for reduction in total PAC-SYM score used to define a clinical response on this 0-4 point scale has not undergone formal appraisal, and its relationship with clinical benefit as perceived by patients has not been defined. AIM: To determine the minimal important difference in PAC-SYM score, and the optimum cut-off value for defining responders. METHODS: The minimal important difference was estimated using data from six international phase 3/4, double-blind, randomised controlled trials of prucalopride in patients with chronic constipation (NCT01147926, NCT01424228, NCT01116206, NCT00485940, NCT00483886, NCT00488137), with anchor- and distribution-based approaches. Five appropriate patient-reported outcomes were selected as anchors. In addition, receiver operating characteristics (ROC) curve analyses were used to investigate responder discrimination for each anchor. RESULTS: Data from 2884 patients were included. Minimal important difference estimates ranged from -0.52 to -0.63 across the five anchors. Estimates were not affected by study location but were consistently lower for rectal symptoms than for abdominal and stool symptoms. Distribution-based estimates were considerably lower than anchor-based estimates. ROC curve analyses showed optimum cut-off scores for discriminating responders to be similar to anchor-based minimal important difference estimates. CONCLUSIONS: Anchor-based methods gave consistent results for the minimal important difference, at approximately -0.6, and this value was close to the ROC-determined optimal cut-off scores for responder discrimination. This value could be considered in clinical practice. A slightly more conservative threshold (eg -0.75) could be used in clinical trials to reduce the placebo response rate.


Subject(s)
Constipation/physiopathology , Randomized Controlled Trials as Topic/methods , Surveys and Questionnaires/standards , Chronic Disease , Constipation/drug therapy , Double-Blind Method , Humans , ROC Curve , Reproducibility of Results
15.
Aliment Pharmacol Ther ; 23(11): 1655-65, 2006 Jun 01.
Article in English | MEDLINE | ID: mdl-16696817

ABSTRACT

AIM: To investigate the efficacy and safety of renzapride, a potent 5-hydroxytryptamine type-4 receptor full agonist and 5-hydroxytryptamine type-3 receptor antagonist in patients with constipation-predominant irritable bowel syndrome. METHODS: In this dose-escalating pilot study, 17 patients with constipation-predominant irritable bowel syndrome received placebo, renzapride 2 mg o.d. and renzapride 2 mg b.d. sequentially for 28 days. Response was determined by radio-opaque marker measurement of overall gastrointestinal and segmental colonic transit and patients' assessment of their irritable bowel syndrome symptoms. RESULTS: Renzapride reduced mean overall gastrointestinal transit time (placebo, 2.9 +/- 1.6 days; renzapride 2 mg o.d., 2.6 +/- 1.4 days; renzapride 2 mg b.d., 1.9 +/- 1.6 days) (P = 0.024) and accelerated segmental colonic transit, with statistically significant differences for renzapride 2 mg b.d. over placebo in caecum/ascending colon (P = 0.019) and descending colon (P = 0.022). Renzapride also reduced abdominal pain, increased the number of pain-free days and improved stool consistency. The frequency of reported adverse events was similar on renzapride and placebo. CONCLUSIONS: Renzapride is well-tolerated, stimulates gastrointestinal transit and improves symptoms in patients with constipation-predominant irritable bowel syndrome, particularly at the 2 mg b.d. dose, where improvements in gastrointestinal symptoms were evident over placebo. This study has established proof of concept and supports further investigation of renzapride in patients with constipation-predominant irritable bowel syndrome.


Subject(s)
Benzamides/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Constipation/drug therapy , Irritable Bowel Syndrome/drug therapy , Serotonin Antagonists/therapeutic use , Adult , Benzamides/adverse effects , Bridged Bicyclo Compounds, Heterocyclic/adverse effects , Dose-Response Relationship, Drug , Female , Gastrointestinal Motility/drug effects , Humans , Male , Middle Aged , Pilot Projects , Serotonin Antagonists/adverse effects , Single-Blind Method , Treatment Outcome
16.
Neurogastroenterol Motil ; 27(6): 805-15, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25808103

ABSTRACT

BACKGROUND: Randomized trials have confirmed the efficacy of prucalopride for the treatment of chronic constipation up to 12 weeks. This study aimed to assess the efficacy of prucalopride over a 24-week period (ClinicalTrials.gov: NCT01424228). METHODS: Adults with chronic constipation and ≤2 spontaneous complete bowel movements (SCBMs)/week were randomized to receive prucalopride 2 mg or placebo daily for 24 weeks. The primary endpoint was the proportion of patients achieving a mean of ≥3 SCBMs/week over the treatment period, assessed using daily e-diaries. Secondary outcomes and safety parameters were assessed throughout the study. KEY RESULTS: Overall, 361 patients were randomized and received prucalopride or placebo. Baseline characteristics were similar in the prucalopride (N = 181) and placebo (N = 180) groups. Mean age was 48.9 years (standard deviation, 16.0) and most patients were women. The proportion of participants achieving the primary endpoint was not statistically different between the prucalopride and placebo groups (25.1% vs 20.7%; p = 0.367). There was also no statistically significant difference between groups over the first 12-week period (prucalopride, 25.1%; placebo, 20.1%; p = 0.341). There were no statistically significant differences between groups for most secondary endpoints. No new safety concerns were identified. CONCLUSIONS & INFERENCES: This trial did not show statistically significant improvements in primary or secondary outcomes with prucalopride compared with placebo over 24 or 12 weeks. This is in contrast to the results of four previous 12-week trials, which demonstrated prucalopride to be significantly more effective than placebo. An extensive evaluation did not provide an explanation for the null efficacy results of this study.


Subject(s)
Benzofurans/therapeutic use , Constipation/drug therapy , Serotonin 5-HT4 Receptor Agonists/therapeutic use , Adult , Aged , Chronic Disease , Double-Blind Method , Female , Humans , Longitudinal Studies , Male , Middle Aged , Treatment Outcome
17.
Neurogastroenterol Motil ; 27(2): 258-68, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25530111

ABSTRACT

BACKGROUND: Approximately, 20-30% of patients with gastro-esophageal reflux disease (GERD) experience persistent symptoms despite treatment with proton pump inhibitors (PPIs). These patients may have underlying dysmotility; therefore, targeting gastric motor dysfunction in addition to acid inhibition may represent a new therapeutic avenue. The aim of this study was to assess the pharmacodynamic effect of the prokinetic agent revexepride (a 5-HT4 receptor agonist) in patients with GERD who have persistent symptoms despite treatment with a PPI. METHODS: This was a phase II, exploratory, multicenter, randomized, placebo-controlled, double-blind, parallel-group study in patients with GERD who experienced persistent symptoms while taking a stable dose of PPIs (ClinicalTrials.gov identifier: NCT01370863). Patients were randomized to either revexepride (0.5 mg, three times daily) or matching placebo for 4 weeks. Reflux events and associated characteristics were assessed by pH/impedance monitoring and disease symptoms were assessed using electronic diaries and questionnaires. KEY RESULTS: In total, 67 patients were enrolled in the study. There were no significant differences between study arms in the number, the mean proximal extent or the bolus clearance times of liquid-containing reflux events. Changes from baseline in the number of heartburn, regurgitation, and other symptom events were minimal for each treatment group and no clear trends were observed. CONCLUSIONS & INFERENCES: No clear differences were seen in reflux parameters between the placebo and revexepride groups.


Subject(s)
Benzofurans/therapeutic use , Gastroesophageal Reflux/drug therapy , Proton Pump Inhibitors/therapeutic use , Serotonin 5-HT4 Receptor Agonists/therapeutic use , Adolescent , Adult , Aged , Benzofurans/adverse effects , Double-Blind Method , Esophageal pH Monitoring , Female , Gastroesophageal Reflux/complications , Humans , Male , Middle Aged , Serotonin 5-HT4 Receptor Agonists/adverse effects , Treatment Outcome , Young Adult
18.
Neurogastroenterol Motil ; 15(5): 447-55, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14507346

ABSTRACT

In functional dyspepsia, abnormal intragastric distribution of a test meal has been identified but has never been correlated to any symptom pattern. The aim of this study was to compare the intragastric distribution of a meal between functional dyspepsia patients and controls, and to correlate distribution with symptom patterns, using scintigraphic gastric emptying studies. In forty patients with functional dyspepsia and 29 healthy volunteers, scintigraphic planar images were obtained immediately after ingestion of a mixed radiolabelled test meal and every 20 min for 2 h. The images of the stomach were divided into proximal and distal compartments. The mean intragastric distribution was similar in patients and controls. Over the whole test, 18 (45%) and 20 (50%) patients had a distal redistribution of the solid and liquid phase of the meal, respectively, while proximal retention of these phases was found in 13 (33%) and 9 (23%) patients. Early satiety was associated with early distal redistribution of the liquid phase and fullness was associated with late proximal retention. This study shows similar intragastric distribution of a test meal in health and functional dyspepsia. Within the patient group, an association between abnormal intragastric distribution patterns and symptom profiles was found, which might be related to different pathophysiological mechanisms.


Subject(s)
Dyspepsia/diagnostic imaging , Dyspepsia/physiopathology , Food/standards , Gastrointestinal Transit/physiology , Adult , Analysis of Variance , Chi-Square Distribution , Confidence Intervals , Female , Gastric Emptying/physiology , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Prospective Studies , Radioimmunodetection/methods , Reference Standards
19.
Pancreas ; 17(2): 187-93, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9700952

ABSTRACT

Bowel rest during treatment of acute pancreatitis deprives the gut of nutrients and affects its structure and function. Enteral feeding is usually performed late in the course of acute pancreatitis and therefore cannot prevent intestinal barrier dysfunction and possible bacterial translocation. To assess the effect of early enteral nutrition we performed a prospective study on 21 patients (11 males/10 females) presenting with severe acute pancreatitis (13 biliary, 6 alcoholic, and 2 miscellaneous). Severity was established by a mean Ranson score of 3.57. All but one patient could be fed through a double-lumen nasogastrojejunal tube within 60 h after admission. No significant complication of the technique was observed. We conclude that early jejunal feeding can be used safely in severe acute pancreatitis. Further comparative studies are necessary to demonstrate any superiority to total parenteral nutrition.


Subject(s)
Enteral Nutrition , Pancreatitis/therapy , Acute Disease , Adult , Aged , Aged, 80 and over , Bacterial Translocation/physiology , C-Reactive Protein/analysis , Endoscopy, Digestive System/methods , Feasibility Studies , Female , Humans , Intubation, Gastrointestinal , Jejunostomy , Male , Middle Aged , Pancreatitis/pathology , Prospective Studies
20.
Gastrointest Endosc Clin N Am ; 6(4): 819-32, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8899412

ABSTRACT

Pharmacologic treatment of bleeding gastrointestinal arteriovenous malformations is difficult. These lesions should be treated pharmacologically only when endoscopic treatment is not successful and bleeding persists or when the lesions cannot be treated endoscopically due to their localization, mainly in the small bowel. These are only a limited number of studies available on the medical treatment of bleeding arteriovenous malformations. There is considerable evidence, however, that a combination of estrogens and progestagens significantly reduces the bleeding frequency and intensity and also the transfusion requirements in patients with high transfusion need. A few other drugs have been tried in patients with bleeding gastrointestinal arteriovenous malformations: danazol, octreotide, desmopressin, and aminocaproic acid. The experience with these drugs, however, is limited to case reports or to small series of patients.


Subject(s)
Arteriovenous Malformations/drug therapy , Arteriovenous Malformations/surgery , Clinical Trials as Topic , Endoscopy , Humans , Prognosis
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