Philip Caenepeel - Academia.edu (original) (raw)

Papers by Philip Caenepeel

Journal of Crohn's and Colitis Supplements, 2008

7 assessed the ability of adalimumab to maintain remission and response in infliximab-failure pat... more 7 assessed the ability of adalimumab to maintain remission and response in infliximab-failure patients who completed the 4-week GAIN trial through 1 year of therapy in an ongoing open-label extension study. Materials and methods: As previously reported, 1 325 patients with Crohn' s disease who failed infliximab therapy enrolled in GAIN and were randomized to receive induction adalimumab 160/80 mg at Weeks 0 and 2 or placebo. At Week 4, all patients were eligible to enter an open-label extension during which they received open-label adalimumab 40 mg every other week. Patients could switch to weekly dosing for flares (increase in Crohn' s Disease Activity Index [CDAI] ≥70 points compared with Week 4 and CDAI>220) or non-response (CDAI decrease <70 points from baseline). Post-hoc analyses of maintenance of remission (CDAI<150) and response (drop in CDAI ≥70 or 100 [CR-100] points) were performed on both the intention-totreat (all patients entering the open-label extension) and responder (CR-70 at Week 4 of GAIN) populations. Results: A total of 310 patients enrolled in the open-label extension, and 126 patients were responders. Remission/response results are shown for all patients who entered the open-label extension .

The American journal of gastroenterology, 2011

Functional dyspepsia (FD) is a heterogeneous disorder with different pathophysiological mechanism... more Functional dyspepsia (FD) is a heterogeneous disorder with different pathophysiological mechanisms underlying the symptom pattern, but little is known about its clinical course. The aims of this study were to study the long-term evolution of symptoms in a clinical FD population and to identify factors associated with outcome. FD patients who previously underwent gastric function testing and filled out a dyspepsia symptom score (DSS) were contacted. At follow-up, patients indicated whether symptoms had worsened, remained unchanged, improved, or disappeared. Anxiety and depression, DSS, chronic fatigue symptoms, irritable bowel syndrome (IBS) comorbidity, and FD-specific quality of life (QoL) were assessed using mailed questionnaires. Bivariate associations between different patient characteristics and DSS and QoL at follow-up were tested; multiple linear regression was used to identify factors associated with the outcomes, both longitudinally and cross-sectionally. Data were obtained...

A new nude-mouse metastasizing orthotopic transplant model of human small-cell carcinoma of the l... more A new nude-mouse metastasizing orthotopic transplant model of human small-cell carcinoma of the lung is described. Histologically-intact human small-cell lung tumors were transplanted to the left lung of nude mice via a thoracotomy procedure we have developed. The transplanted tumors grew extensively locally and metastasized to the opposite lung, lymph nodes and other clinically-relevant sites. The results described indicate the model developed could have clinical relevance and contrasts with models of small-cell carcinoma constructed with injections of cell suspensions which result in few or no metastases.

The American journal of gastroenterology, 2003

The relationship between functional dyspepsia and delayed gastric emptying of solids or liquids i... more The relationship between functional dyspepsia and delayed gastric emptying of solids or liquids is still unclear. The aim of the present study was to investigate in dyspeptic patients the prevalence of delayed gastric emptying for solids or for liquids and to investigate the relationship to the dyspepsia symptom pattern. In 392 and 330 patients with functional dyspepsia, the solid and liquid gastric emptying, respectively, was measured using breath tests, and the severity of eight dyspeptic symptoms was scored. Gastric emptying of solids and liquids were delayed in 23% and 35% of the patients. Multivariate analysis showed that the presence of vomiting and postprandial fullness was associated with delayed solid emptying (OR 2.65, 95% CI = 1.62-4.35 and OR 3.08, 95% CI = 1.28-9.16, respectively). Postprandial fullness was also associated with the risk of delayed liquid emptying when symptom was present (OR 3.5, 95% CI = 1.57-8.68), relevant or severe (OR 2.504, 95% CI = 1.41-4.65), an...

The American journal of gastroenterology, 2004

Epidemiological studies suggest considerable overlap between functional dyspepsia (FD) and irrita... more Epidemiological studies suggest considerable overlap between functional dyspepsia (FD) and irritable bowel syndrome (IBS). The aim of the present study was to investigate whether coexisting IBS is also associated with symptom pattern or pathophysiology in FD. In 309 consecutive FD patients (207 women, age 42 +/- 0.8 yr), questionnaires were used to assess the dyspepsia symptom pattern and the Rome II criteria for IBS. The overall symptom severity was calculated adding the severity score (0-3, 0 = absent, 3 = severe) of eight dyspepsia symptoms. All patients underwent Helicobacter pylori testing, gastric barostat to determine sensitivity to distention and accommodation to a meal, and gastric emptying breath test. Fifty-four percent of the patients had FD alone, whereas 46% had FD + IBS. FD + IBS patients were more likely to be female (75%vs 60%, p < 0.01) and to have a greater weight loss (5.4 +/- 0.6 vs 3.5 +/- 0.4 kg, p < 0.05). Coexisting IBS did not increase the risk of hav...

The American journal of gastroenterology, 2012

Several studies have reported symptom relief in gastro-esophageal reflux disease (GERD) patients ... more Several studies have reported symptom relief in gastro-esophageal reflux disease (GERD) patients treated with radiofrequency delivery (Stretta procedure) at the gastro-esophageal junction (GEJ), but the mechanism underlying this improvement is unclear. The objective of this study was to test the hypothesis that Stretta alters GEJ resistance. We conducted a double-blind randomized cross-over study of Stretta and sham treatment. Consecutive GERD patients were included in the study. The study was conducted in a tertiary care center. Patients underwent two upper gastrointestinal endoscopies with 3 months interval, during which active or sham Stretta treatment was performed in a randomized double-blind manner. Symptom assessment, endoscopy, manometry, 24-h esophageal pH monitoring, and a distensibility test of the GEJ were done before the start of the study and after 3 months. Barostat distensibility test of the GEJ before and after administration of sildenafil was the main outcome measu...

The Lancet, 2008

Background Most patients who have active Crohn's disease are treated initially with corticosteroi... more Background Most patients who have active Crohn's disease are treated initially with corticosteroids. Although this approach usually controls symptoms, many patients become resistant to or dependent on corticosteroids, and long exposure is associated with an increased risk of mortality. We aimed to compare the eff ectiveness of early use of combined immunosuppression with conventional management in patients with active Crohn's disease who had not previously received glucocorticoids, antimetabolites, or infl iximab.

Journal of Crohn's and Colitis, 2007

Background and aim: Although the efficacy of maintenance remission therapy in ulcerative colitis ... more Background and aim: Although the efficacy of maintenance remission therapy in ulcerative colitis (UC) has been proved in many studies, little is known about its possible effect on the extent of the disease. The aim of the present multicenter Belgian study was to evaluate the potential role of UC maintenance therapy on the colonic extension of the disease. Materials and methods: A total of 98 patients, 56 males, 42 females, mean age 52 years, range 22-82 years, from 12 medical centers in Belgium, with an acute exacerbation of wellestablished, endoscopically and histologically proven left-sided UC, were included. The colonic extension was endoscopically determined at the time of the initial diagnosis and at the actual

Gut, 2008

A subset of functional dyspepsia (FD) patients report meal-related symptoms, possibly representin... more A subset of functional dyspepsia (FD) patients report meal-related symptoms, possibly representing a pathophysiologically homogeneous subgroup. The aim of the present study was to establish the time-course of symptoms in relation to meal ingestion, and to assess the relationship between self-reported meal-related symptoms and pathophysiological mechanisms in FD. 218 FD patients (149 women, mean (SEM) age 39 (1) years) filled out a symptom questionnaire, including meal-induced aggravation. All patients underwent a gastric emptying breath test with severity (0-4) scoring of six symptoms (pain, fullness, bloating, nausea, burning and belching) at each sampling (15 min interval for 4 h). In 129 patients, gastric sensitivity and accommodation were assessed by barostat. The intensity of each FD symptom was significantly increased 15 min after the meal, compared with the premeal score, and remained elevated until the end of the measurement period (all p<0.05). The time-course of individual symptoms varied, with early peaks for fullness and bloating, intermediate peaks for nausea and belching, and late peaks for pain and burning. Meal-induced aggravation was reported by 79% of patients, and in these patients postprandial fullness, which peaked early, was the most intense symptom. In patients without self-reported meal-induced aggravation, epigastric pain, which had a delayed peak, was the most intense symptom and they had a lower prevalence of gastric hypersensitivity (27.5% vs 7.7%). Meal ingestion aggravates FD symptoms in the vast majority of patients, with symptom-specific time-courses. Postprandial fullness is the most severe symptom in patients reporting aggravation by a meal, while it is pain in those not reporting meal-related symptoms.

Gut, 2003

Aims: Impaired gastric accommodation is a major pathophysiological mechanism in functional dyspep... more Aims: Impaired gastric accommodation is a major pathophysiological mechanism in functional dyspepsia. The aim of the present work was to assess a satiety drinking test in the evaluation of accommodation in health and dyspepsia. Methods: Twenty five controls and 37 severely dyspeptic patients seen at a tertiary care centre completed a dyspepsia questionnaire, and gastric emptying and gastric barostat studies. The amount of liquid meal ingested at maximum satiety during a slow satiety drinking test was determined. In controls, we studied the influence of caloric density and of pharmacological agents that influence accommodation. Results: In patients, satiety scores were higher and maximum satiety occurred at lower calories (542 (50) v 1508 (53) kcal; p<0.0001). Six patients had required nutritional support, but excluding these did not alter the correlations. With increasing severity of early satiety, less calories were ingested at maximum satiety. In multivariate analysis, the amount of calories was significantly correlated to accommodation but not to gastric emptying or sensitivity. Sensitivity and specificity of the satiety test in predicting impaired accommodation reached 92% and 86%, respectively. At different caloric densities, ingested volume rather than caloric load determined maximum satiety. Pharmacological agents (sumatriptan, cisapride, erythromycin) affected the satiety test according to their effect on accommodation. Conclusion: A slow caloric drinking test can be used to evaluate accommodation and early satiety. It provides a non-invasive method of predicting impaired accommodation and quantifying pharmacological influences on accommodation.

Gut, 2007

Idiopathic gastroparesis is a syndrome characterised by severely delayed gastric emptying of soli... more Idiopathic gastroparesis is a syndrome characterised by severely delayed gastric emptying of solids without an obvious underlying organic cause. Although delayed gastric emptying is traditionally considered the mechanism underlying the symptoms in these patients, poor correlations with symptom severity have been reported. To investigate proximal stomach function and to study the correlation of delayed gastric emptying and proximal stomach dysfunction with symptom pattern and severity in idiopathic gastroparesis. 58 consecutive patients (19 men, mean (standard deviation) age 41 (2) years) with severely delayed solid gastric emptying (gastric half-emptying time (t(1/2))>109 min) without an organic cause were recruited. They filled out a symptom-severity questionnaire and underwent a gastric barostat study for assessment of gastric sensitivity and accommodation. Correlation of these mechanisms with symptom pattern and overall symptom severity (sum of individual symptoms) was analysed. At two different cut-off levels for gastric emptying (upper limit of normal t(1/2) up to 1.5 and 2 times), no significant change in symptom pattern occurred. 25 (43%) patients had impaired accommodation, and this was associated with higher prevalence of early satiety (p<0.005) and weight loss (p = 0.009). 17 (29%) patients had hypersensitivity to gastric distension, and this was associated with higher prevalences of epigastric pain (p = 0.005), early satiety (p = 0.04) and weight loss (p<0.005). Overall symptom severity was not correlated with gastric emptying or accommodation, but only with sensitivity to gastric distension (R = -0.3898, p = 0.003) and body weight (R = -0.4233, p = 0.001). In patients with idiopathic gastroparesis, the symptom pattern is determined by proximal stomach dysfunction rather than by the severity of delayed emptying.

$Research paper thumbnail of Endoluminal Fundoplication (Esophyx®) in GERD Patients Refractory to PPI Therapy: Effect On Symptoms, PPI Use and Distensibility$

Gastrointestinal Endoscopy, 2009

Gastrointestinal Endoscopy, 2005

Gastroenterology, 2002

Abbreviations used in this paper: 5-HT 1 , 5-hydroxytryptamine 1 ; L-NMMA, N G -monomethyl-L-argi... more Abbreviations used in this paper: 5-HT 1 , 5-hydroxytryptamine 1 ; L-NMMA, N G -monomethyl-L-arginine; MDP, minimal distending pressure; NOS, nitric oxide synthase; t 1 ⁄2, half emptying time.

Gastroenterology, 2001

Abbreviations used in this paper: CI, confidence interval; MDP, minimal distending pressure; OR, ... more Abbreviations used in this paper: CI, confidence interval; MDP, minimal distending pressure; OR, odds ratio; t1/2, half emptying time.

Gastroenterology, 2004

Background & Aims: Studies in health have shown that tension-sensitive mechanoreceptors mediate s... more Background & Aims: Studies in health have shown that tension-sensitive mechanoreceptors mediate sensitivity to gastric distention. A role for these mechanoreceptors in perception or symptoms in hypersensitive functional dyspepsia (FD) has not been established. Tension-sensitive mechanoreceptors are activated during phasic contractions and inactivated during gastric relaxation. The aim of the present study was to investigate whether hypersensitive FD patients perceive spontaneous changes in fundic wall tension and whether fundus-relaxing drugs decrease sensitivity to gastric distention and meal-related symptoms. Methods: Fifty patients were selected after a barostat study established gastric hypersensitivity. In 12 patients, an intragastric balloon was inflated with a fixed volume just below perception thresholds and patients were asked to indicate changes in perception on a keypad, and the relationship between perception and contractions was analyzed. In 20 patients, we studied the influence of the fundus-relaxing drug sumatriptan on sensitivity to gastric distention. In, respectively, 10 and 8 patients, we studied the influence of the fundus-relaxing drugs sumatriptan and clonidine on meal-related symptoms. Results: The majority of patients had a statistically significant association between perception and phasic isovolumetric contractions. Pretreatment with sumatriptan increased both pressures and volumes needed to induce first perception and discomfort. Pretreatment with sumatriptan and clonidine both significantly decreased meal-induced symptoms. Conclusions: Patients with hypersensitivity to gastric distention perceive isovolumetric phasic contractions of the proximal stomach. Fundus-relaxing drugs decrease sensitivity to gastric distention and decrease meal-induced symptoms in these patients. The findings are compatible with involvement of tension mechanoreceptors in symptom generation in hypersensitive FD.

Gastroenterology, 2009

BACKGROUND AND AIMS: Chronic or acute recurrent pancreatitis is considered to a complex multigeni... more BACKGROUND AND AIMS: Chronic or acute recurrent pancreatitis is considered to a complex multigenic disease. « Genetic » pancreatitis (GP) is associated with mutations mainly in the cationic trypsinogen (PRSS1), SPINK1 and CFTR genes. Natural history of GP remains poorly documented. The aims of this study were to assess genetic, clinical and morphological characteristics of patients with GP. METHODS: Inclusion criteria were the presence of PRSS1, CFTR and SPINK gene mutations in patients with idiopathic recurrent or chronic pancreatitis. Genetic testing was performed in 331 probands referred to our centre from 1999 until 2008. Whole coding region of PRSS1 was analysed while a specific exon 3 scanning for SPINK1 and screening for a panel of 36 common CFTR causing mutations were done. Further complete CFTR sequencing (sequencing and MLPA) was performed in case of positive targeted panels. RESULTS: Seventeen of 331 pts (5.1%) had a disease causing mutation in PRSS1, another 9.8% (15/152) had SPINK1 substitutions (p.N34S) and 37/331 (11%) had CFTR by mutation targeted testing. Of the 37 pts with a CFTR mutation 3 carried a SPINK1 and four a PRSS1 mutation. Moreover 1 pt was transheterozygote PRSS1/SPINK1. Median ages at first symptom and diagnosis, were 29 [range: 3-65], 36 [3-66] and 30 [1-84)] y, respectively. Follow-up now extends to a median of 6.8 y. GP was responsible for pancreatic pain in all patients, with a mean of 4.8 [0-15] acute pancreatitis attacks, responsible for 2 [0-15] hospitalisations accounting for 14 [0-60] days. Smoking was observed in 13 pts (21.6%). Severity of chronic pancreatitis was calculated with the M-ANNHEIM score with 17 pts with minor, 26 increased, 8 advanced, 5 marked and 3 exacerbated severities. Calcifications were seen in 44.6%, endocrine insufficiency in 18.9% and exocrine insufficiency in 25.4%. Endoscopic treatment was done in 45% (sphincterotomy in 27, stone extraction in 11, and stenting in 25) and surgery in 5 (8.2%). Interestingly, 7 pts (11.5%) had also a pancreas divisum, 6 associated with CFTR mutations and 1 with PRSS1. Five pts presented with a cancer (2 adenocarcinoma, 2 malignant IMPT, 1 glucagonoma) during follow-up, all of them with a CFTR mutation and heavy smoking habits. CONCLUSIONS: In total, multistep testing of PRSS1, SPINK1 and CFTR genes identified genetic variants in only 19% of patients considered clinically as candidate for genetic testing, a rate lower than previously reported. Our cohort is characterized by a high rate of cancer, mainly associated with CFTR mutations and smoking, rather than PRSS1 mutations that should be more typically associated with an increased risk of cancer.

Gastroenterology, 2008

with H. pylori were enrolled. C-14 Urea breath test and rapid urease test were done to confirm th... more with H. pylori were enrolled. C-14 Urea breath test and rapid urease test were done to confirm the presence of H. pylori infection before the enrollment. Gastric biopsies from both antrum and body were taken for rapid urease test, histology and polymerase chain reactionrestriction fragment length polymorphism analysis (PCR-RFLP). Forward primer (5'-TGGGACTGATGGCGTGAGGG -3') and reverse primer (5'-AAGGGCGTTTTTAGATTTTT -3') prepared from the urease gene C gene were used to amplify 820 bp gene product and Sau-3 and Hha I restriction enzymes for RFLP analysis. RESULTS: There were ninety-five patients with 68 (72%) males. On endoscopy, 53(56%) had gastric antral and 39(41%) had pangastric erythema. and 3(3%) had duodenal ulcer. H. pylori associated chronic active gastritis on histology was present in 76(80%). PCR-RFLP patterns were similar in 77(81%) on both antrum and body and different in 18(19 %). On endoscopy, antral gastric erythema was present in 44(79%) with same RFLP pattern from both antrum and body and 12(21%) with different RFLP patterns, while pangastric erythema was present in 33(85%) with same RFLP pattern and 6(15%) with different RFLP patterns on bothsides (p=0.46).On histology, chronic active gastritis was associated in 61(79%) patients with single RFLP pattern and in 15(83%) with different H. pylori strain (p=0.69) on both antrum and body. Patients with corpus dominant gastritis had chronic active gastritis in 16(21%) with single RFLP pattern and 3(17%) with multiple RFLP patterns p=0.89. CONCLUSION: Almost one fifth of dyspeptic patients had H. pylori infection with more than one strain in our series. This might contribute to lack of response to treatment especially in patients having H. pylori infection with multiple strains.