Position statement on how can we can implement the Greendeal in our gastrointestinal and gastrointestinal endoscopy department in Belgium.

The importance to reach the target to be carbon net zero by 2050, as presented by the European Commission in the European Green Deal, cannot be overestimated. In a current endoscopy world, where single use has found its place and techniques are constantly evolving, it will be a challenge to reach these goals. How can we reconcile this evolution to a carbon neutral status by 2050 without compromising patients care, clinical standards and training needs? The European Society of Gastrointestinal Endoscopy (ESGE) together with the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) recently published a position statement (1) whereas in the UK there is the work from the green endoscopy group (2) in line with the strategy of the British Society of Gastroenterology (BSG) on sustainability (3). In Flanders, a project called "greendeal in duurzame zorg" had its kick off in March 2023 (4) so it is about time that we in Belgium, as gastroenterologists, start with tangible actions to a more sustainable daily practice. We wrote this position statement in cooperation with the Vlaamse Vereniging voor Gastro-Enterologie (VVGE), the Société royale belge de Gastro-entérologie (SRBGE) and the Belgian Society of Gastrointestinal Endoscopy (BSGIE). We will also work together in the coming years to continue to motivate our members to work on these initiatives and to co-opt new projects within the framework of the greendeal.

Belgian consensus on irritable bowel syndrome.

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.

Unsuccessful transjugular intrahepatic portosystemic shunt for a patient with right heart failure and portal hypertension.

A 60-year-old women with a history of congenital pulmonary valve stenosis developed right heart failure, cardiac cirrhosis and end-stage renal disease requiring renal replacement therapy. Cirrhosis was complicated by portal hypertension, resulting in intractable gastro-intestinal bleedings despite optimal treatment with beta-blockers and endoscopic band ligation. Because of fears for worsening right heart failure, a decision for placement of a transjugular intrahepatic portosystemic shunt (TIPS) was initially turned down. However, as intractable bleeding problems persisted and caused heavy transfusion needs, TIPS was ultimately performed as a rescue procedure. Although TIPS successfully reduced the hepatic venous pressure gradient from 16 mmHg to 4 mmHg, portal pressure remained high at 14 mmHg because of persisting right heart failure with elevated central venous pressure. Hepatic encephalopathy soon developed after TIPS placement and culminated in multi-organ failure after another episode of gastro-intestinal bleeding. At this point, the family of the patient decided to withdraw care and the patient died subsequently. This case illustrates how important it is to diagnose and optimally treat right heart failure before cardiac cirrhosis with its impending complications emerges. Although TIPS may effectively treat complications of portal hypertension in the context of cirrhosis, persisting right heart failure may abrogate its beneficial effects.

Mucocutaneous leishmaniasis of the nose: a case report.

Mucocutaneous leishmaniasis of the nose: a case report. Leishmaniasis is a parasitic infection that is rarely seen in Belgium. The majority of new diagnoses are seen in patients living in or visiting endemic regions, which are mostly developing countries. Here we describe the case of a 60-year-old male patient who was referred to an ENT specialist because of an erythematous swelling of the left side of the nose tip, which had persisted for 3 months. Biopsies showed the presence of leishmaniasis. This case report alerts ENT physicians that leishmaniasis is part of the differential diagnosis in patients who present with an uncommon persistent lesion in the head and neck region and who have travelled to endemic regions or are immunodeficient.

A pilot study of the effects of the somatostatin analog pasireotide in postoperative dumping syndrome.

BACKGROUND: Dumping syndrome is characterized by distinct pathophysiological features such as postprandial increase in hematocrit (HT) and pulse rate (PR) and delayed hypoglycemia (HG). Treatment is based on dietary measures and somatostatin analogs (SA), but current SAs have incomplete efficacy, possibly through limited affinity for various somatostatin receptor subtypes. We evaluated the effect of pasireotide, a novel SA with high affinity for 4/5 human somatostatin receptors, on pathophysiological events and symptoms in dumping. METHODS: Randomized double-blind placebo-controlled cross-over study of nine patients (six women, 47 ± 4 years) with postoperative dumping. Baseline measurements included oral glucose tolerance testing (OGTT), abdominal ultrasound, and dumping symptom severity score (DSSS). Patients were treated for 2 weeks with placebo or pasireotide 300 µg s.c. t.i.d. with a 1-week wash-out in a randomized fashion. On day 13 and 14 of each treatment OGTT, DSSS, and solid and liquid gastric emptying (GE) were obtained. KEY RESULTS: Baseline OGTT was pathological in all patients based on PR (n = 5), HT (n = 1) or HG (n = 7). Compared to placebo, pasireotide suppressed the increase in PR (17.1 ± 2.8 vs 8.2 ± 3.5 bpm; p < 0.05) and late HG (nadir glycemia 55.6 ± 4.3 vs 83.3 ± 9.5 mg/dL; p = 0.007), increased peak glycemia (294.1 ± 33.3 vs 221.0 ± 23.1 mg/dL; p = 0.001) and delayed GE of solids (t1/2 83 ± 23 vs 43 ± 9 min; p = 0.05) and liquids (t1/2 70 ± 10 vs 40 ± 4 min, p = 0.05). The differences in DSSS did not reach statistical significance. Two patients dropped out because of adverse gastrointestinal events under pasireotide. CONCLUSIONS & INFERENCES: Pasireotide affects pathophysiological features of both early and late dumping syndrome.

A double-blind sham-controlled study of the effect of radiofrequency energy on symptoms and distensibility of the gastro-esophageal junction in GERD.

OBJECTIVES: 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. METHODS: 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. RESULTS: Barostat distensibility test of the GEJ before and after administration of sildenafil was the main outcome measure. In all, 22 GERD patients (17 females, mean age 47±12 years) participated in the study; 11 in each group. Initial sham treatment did not affect any of the parameters studied. Three months after initial Stretta procedure, no changes were observed in esophageal acid exposure and lower esophageal sphincter (LES) pressure. In contrast, symptom score was significantly improved and GEJ compliance was significantly decreased. Administration of sildenafil, an esophageal smooth muscle relaxant, normalized GEJ compliance again to pre-Stretta level, arguing against GEJ fibrosis as the underlying mechanism. CONCLUSIONS: The limitation of this study was reflux evaluation did not include impedance monitoring. In this sham-controlled study, Stretta improved GERD symptoms and decreased GEJ compliance. Decreased GEJ compliance, which reflects altered LES neuromuscular function, may contribute to symptomatic benefit by decreasing refluxate volume.

Rumination or belching-regurgitation? Differential diagnosis using oesophageal impedance-manometry.

BACKGROUND: Rumination is an eating disorder clinically suspected in the presence of chronic regurgitation of recently ingested food with subsequent re-mastication and swallowing. Oesophageal manometry is currently used to confirm the diagnosis, however, it is difficult to distinguish rumination from postprandial belching-regurgitation, being the manometric pattern identical in both situations. Oesophageal impedance allows recognition between liquid and gas gastro-oesophageal reflux. Our aims were (i) to improve diagnosis of rumination using combined impedance-manometry (ii) to assess the gastro-oesophageal pressure-flow pattern in rumination events. METHODS: Sixteen patients with clinically suspected rumination underwent impedance-manometry monitoring for 1 h after a solid liquid meal. Manometry was first analysed blindly to the impedance pattern. All events marked by the patients and straining episodes were identified. After the manometric analysis, impedance tracings were unblinded and each straining episode was analysed for presence of liquid and/or gas oesophageal retrograde flow. Only rumination events were included for additional evaluation. KEY RESULTS: Postprandial manometry showed a pattern compatible with rumination in 12/16 patients. In total, impedance-manometry confirmed the clinical diagnosis of rumination in eight of the 16 patients with clinical suspicion of rumination. In 102 clearly identified rumination events, the onset of gastric strain (manometry) occurred before the onset of oesophageal liquid retroflow (impedance) in 58% of cases or simultaneously in 37% of cases. In most cases (86%), oesophageal retrograde flow started after an initial increase in abdominal pressure but before the peak gastric strain pressure. CONCLUSIONS & INFERENCES: Postprandial impedance-manometry monitoring improves diagnosis of rumination because it allows distinction between rumination and postprandial belching and regurgitation. During rumination, oesophageal liquid retrograde flow is first driven by an early small rise in intragastric pressure preceding the peak pressure observed during straining.

Relationship between symptom pattern, assessed by the PAGI-SYM questionnaire, and gastric sensorimotor dysfunction in functional dyspepsia.

The patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) questionnaire was recently developed and validated for the evaluation of therapeutic responsiveness in functional dyspepsia (FD). Functional dyspepsia is a heterogeneous disorder, with different pathophysiological mechanisms underlying the symptom pattern. The relationship between PAGI-SYM scores and putative pathophysiological mechanisms has not been studied. The aim of this study was to evaluate the relationship between PAGI-SYM subscales and gastric emptying, gastric sensitivity and gastric accommodation in FD. A total of 161 consecutive FD patients underwent Helicobacter pylori (HP), gastric barostat and standardized gastric emptying testing (n = 126), and completed the PAGI-SYM questionnaire. Relationships between scores for the six subscales (heartburn/regurgitation, nausea/vomiting, fullness/satiety, bloating, upper abdominal pain, lower abdominal pain) and gastric function were analysed using Pearson's linear correlation, multiple regression analysis, chi-square and Student's t-tests. Gastric emptying was significantly correlated with scores for heartburn/regurgitation (r = 0.26), nausea/vomiting (r = 0.19), fullness/satiety (r = 0.20), bloating (r = 0.21) and lower abdominal pain (r = 0.22; all P < 0.05). Patients with delayed emptying had significantly higher scores for each of these subscales (all P < 0.05). Discomfort volume during gastric distension was significantly correlated with scores for fullness/satiety (r = -0.27), bloating (r = -0.23), heartburn/regurgitation (r = -0.21), and upper abdominal pain (r = -0.20). Patients with hypersensitivity to distension had significantly higher scores for fullness/satiety (P < 0.05). At different cut-off levels of symptom severities, consistent associations were found between fullness/satiety and gastric discomfort volume, between preprandial volumes and upper abdominal pain, compliance and upper abdominal pain, and between bloating and gastric discomfort volume. Multiple regression analysis revealed that gastric emptying rate contributed significantly to models for the severity of these subscales. The importance of discomfort volume disappeared in favour of gender when sex was included in the model. No significant correlations were found with HP status or with gastric accommodation. PAGI-SYM scores are mainly correlated with gastric emptying rate and with gastric hypersensitivity. Multivariate analysis suggests that the questionnaire may be useful in the evaluation of gastroprokinetics. Its role in the evaluation of drugs that alter gastric sensitivity is less clear.

Influence of abuse history on gastric sensorimotor function in functional dyspepsia.

Patients with functional gastrointestinal disorders have elevated rates of sexual or physical abuse, which may be associated with altered rectal sensorimotor function in irritable bowel syndrome. The aim was to study the association between abuse history and gastric sensorimotor function in functional dyspepsia (FD). We studied gastric sensorimotor function with barostat (sensitivity, compliance and accommodation) and gastric emptying test in 233 consecutive FD patients from a tertiary care centre (162 women, mean age 41.6 +/- 0.9). Patients filled out self-report questionnaires on history of sexual and physical abuse during childhood or adulthood. Eighty-four patients (out of 198, 42.4%) reported an overall history of abuse [sexual and physical in respectively 30.0% (60/200) and 20.3% (42/207)]. FD patients reporting general as well as severe childhood sexual abuse have significantly lower discomfort thresholds during gastric distension [respectively 10.5 +/- 0.4 vs 7.5 +/- 1.0 mmHg above minimal distending pressure (MDP), P = 0.014 and 10.5 +/- 0.4 vs 6.6 +/- 1.2 mmHg above MDP, P = 0.007]. The corresponding intra-balloon volume was also significantly lower (respectively 579 +/- 21 vs 422 +/- 59 mL, P = 0.013 and 579 +/- 19 vs 423 +/- 79 mL, P = 0.033). Gastric accommodation was significantly more pronounced in patients reporting rape during adulthood (91 +/- 12 vs 130 +/- 40 mL, P = 0.016). Abuse history was not associated with differences in gastric emptying. A history of abuse is associated with alterations in gastric sensorimotor function in FD. Particularly sexual abuse, rather than physical abuse, may influence gastric sensitivity and motor function.

Relationship between symptoms and ingestion of a meal in functional dyspepsia.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: 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.

Clinical trial: a randomized-controlled crossover study of intrapyloric injection of botulinum toxin in gastroparesis.

BACKGROUND: Uncontrolled studies suggest benefit of intrapyloric injection of botulinum toxin (botox) for the treatment of gastroparesis, but controlled data are lacking. AIM: To perform a controlled study of botox injection in gastroparesis. METHODS: Twenty-three gastroparesis patients (five men, age 45 +/- 3, 19 idiopathic) underwent two upper endoscopies with 4-week interval, with injection of saline or botox 4 x 25 U in a randomized double-blind-controlled crossover fashion. Before the start of the study and 4 weeks after each treatment, they underwent a solid and liquid gastric emptying breath test with measurement of meal-related symptom scores, and filled out the Gastroparesis Cardinal Symptom Index. Results (mean S.E.M.) were compared using Student's t-test. RESULTS: Twelve patients received botox and 11 saline as the first injection. Significant improvement in emptying and Gastroparesis Cardinal Symptom Index was seen after initial injection of saline or botox. No further improvement occurred after the second injection (respectively, botox and saline). Pooled data for both treatment groups showed no significant difference in improvements of solid t(1/2) (3.4 +/- 7.4 vs. 16.3 +/- 8.3, N.S.) and liquid t(1/2) (8.2 +/- 13.7 vs. 22.5 +/- 7.7, N.S.), meal-related symptom scores or Gastroparesis Cardinal Symptoms Index (GCSI; 6.1 +/- 1.5 vs. 3.8 +/- 1.5, N.S.). CONCLUSION: In a cohort of predominantly idiopathic gastroparesis patients, botox is not superior to placebo in improving either symptoms or the rate of gastric emptying.

Maintenance therapy for ulcerative colitis has no impact on changes in the extent of ulcerative colitis.

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 well-established, 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 flare-up. The mean duration of UC was 93+72 months, median was 84 months, and range was 3-372 months. Active smoking was reported in only 7% of patients, while the majority were no-smokers (63%) or ex-smokers (30%). The median colonic extension at the time of initial diagnosis was 25 cm, range 2-70 cm from the anal merge. Sixty-six percent of the patients had quiescent disease without flare-ups during last year. The χ(2)-test was used for statistical analysis. RESULTS: 29/98 (29.6%) patients had not used any maintenance therapy in the last 3 months before the actual exacerbation. The most commonly used maintenance therapy was 5-ASA (43%), while combined therapy with 5-ASA, corticosteroids or immunosuppresives (mainly azathioprine) in all possible combinations was reported by 29.6% of patients. The extent of UC had not changed in 50.7% and 51.7% of patients, respectively, with and without maintaining therapy (NS, p=0.99). Some degree of regression was observed in, respectively, 21.7% and 20.7% (NS, p=0.99), and some degree of extension in, respectively, 27.5% and 27.6% (NS, p=0.99). Furthermore, no relationship was found between changes in colonic extent and type of maintaining therapy, smoking habits or disease activity during the last year before the acute exacerbation. A tendency of beneficial effect of maintenance therapy on disease extent was observed in patients with continuous active disease of short duration. CONCLUSIONS: According to this multicenter study, maintenance remission therapy for left-sided UC was not found to have a statistically significant effect on colonic extension. Further long-term studies are necessary to confirm these results.

Determinants of symptom pattern in idiopathic severely delayed gastric emptying: gastric emptying rate or proximal stomach dysfunction?

BACKGROUND: 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. AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: In patients with idiopathic gastroparesis, the symptom pattern is determined by proximal stomach dysfunction rather than by the severity of delayed emptying.

Influence of intrapyloric botulinum toxin injection on gastric emptying and meal-related symptoms in gastroparesis patients.

BACKGROUND: Recent observations in limited numbers of patients suggest a potential benefit of intrapyloric injection of botulinum toxin in the treatment of gastroparesis. AIM: To characterize the effect of botulinum toxin on solid and liquid gastric emptying and on meal-related symptoms. METHODS: In 20 gastroparesis patients (17 women, mean age 37 +/- 3 years, three diabetic and 17 idiopathic), gastric emptying for solids and liquids was measured before and one month after intrapyloric botulinum toxin 4 x 25 units. Before the meal and at 15-min intervals up to 240 min postprandially, the patient graded the intensity of six gastroparesis symptoms, and a meal-related severity score was obtained by adding all intensities. Data (mean +/- S.E.M.) were compared using paired Student's t-test. RESULTS: Treatment with botulinum toxin significantly enhanced solid (t(1/2) 132 +/- 16 vs. 204 +/- 35 min, P < 0.05) but not liquid (92 +/- 10 vs. 104 +/- 11 min, N.S.) emptying. This was accompanied by a significant decrease in cumulative meal-related symptom score (73.5 +/- 16.3 vs. 103 +/- 17.1 baseline, P = 0.01) as well as individual severity scores for postprandial fullness, bloating, nausea and belching (all P < 0.001, two-way anova). CONCLUSIONS: Botulinum toxin improves solid but not liquid gastric emptying in gastroparesis, and this is accompanied by significant improvement of several meal-related symptoms.

Prevalence of acid reflux in functional dyspepsia and its association with symptom profile.

AIM: A subset of functional dyspepsia patients respond to acid suppressive therapy, but the prevalence of non-erosive reflux disease in functional dyspepsia and its relevance to symptoms have never been established. The aim of the present study was to study 24 hour pH monitoring in consecutive functional dyspepsia patients. METHODS: A total of 247 patients with dyspeptic symptoms (166 women, mean age 44 (SEM 1) year), with a negative upper gastrointestinal endoscopy and without dominant symptoms of heartburn participated in the study. In all patients, the severity of dyspeptic symptoms and the presence of heartburn was assessed by a questionnaire and a 24 hour oesophageal pH monitoring study was performed. All patients underwent a gastric emptying breath test and in 113 a gastric barostat study was performed. RESULTS: Abnormal pH monitoring (acid exposure >5% of time) was found in 58 patients (23%). Of 21 patients with a positive heartburn questionnaire, 76% had pathological pH monitoring, while this was the case in only 18.5% of patients with a negative heartburn questionnaire. Demographic characteristics and the prevalence of other pathophysiological mechanisms did not differ between heartburn negative patients with normal or abnormal acid exposure. Pathological acid exposure in heartburn negative patients was associated with the presence of epigastric pain (65 v 84%, p<0.005) and of moderate or severe pain (48 v 69%, p = 0.005). CONCLUSION: Pathological oesophageal acid exposure is only present in a subset of heartburn negative functional dyspepsia patients, which are characterised by a higher prevalence of epigastric pain.

Influence of erythromycin on gastric emptying and meal related symptoms in functional dyspepsia with delayed gastric emptying.

BACKGROUND AND AIMS: Although delayed gastric emptying is considered a major pathophysiological mechanism in functional dyspepsia, the efficacy of prokinetic drugs has not been established. Recent studies using macrolide prokinetics were negative but receptor desensitisation may have played a role. The aim of the present study was to evaluate the influence on meal induced symptoms of acutely administered erythromycin in patients with gastroparesis. METHODS: In 20 patients with functional dyspepsia, gastric emptying was studied twice using the (14)C octanoic acid and (13)C glycin breath test to establish the reproducibility of the test. Breath samples were taken before the meal and at 15 minute intervals for a period of 240 minutes postprandially. At each breath sampling, the patient was asked to grade the intensity (0-3) of six dyspeptic symptoms. Twenty four patients (three men, mean age 43.5 (3) years) with dyspeptic symptoms and delayed gastric emptying were studied twice after pretreatment with saline or erythromycin intravenously. RESULTS: Meal related symptom severity scores were reproducible. Treatment with erythromycin significantly enhanced solid and liquid gastric emptying (t(1/2) 146 (27) v 72 (7) minutes, respectively (p<0.01), and 87 (6) v 63 (5) minutes (p<0.001)). Only the severity of bloating was significantly improved by erythromycin (23 (3.9) v 14.5 (2.7); p<0.01); all other symptoms and the cumulative meal related symptom score were not altered by erythromycin. CONCLUSIONS: In a setting where desensitisation played no role, erythromycin enhanced gastric emptying was not associated with a beneficial effect on meal related symptom severity.

The role of tension receptors in colonic mechanosensitivity in humans.

BACKGROUND: Perception of colonic distension, which is enhanced in a subset of patients with irritable bowel syndrome, requires activation of mechanoreceptors. In animal studies, distension activates both in series ("tension") and in parallel ("elongation") mechanoreceptors. During active contractions against a fixed volume balloon, tension receptors are activated without elongation of receptor activation. AIM: To evaluate the role of tension receptors in the perception of mechanical stimuli from the colon in healthy subjects. METHODS: A 700 ml balloon connected to a barostat-manometer assembly was placed in the descending colon of 10 healthy subjects. After volume controlled distension (50 ml/2 minutes) to assess the first perception threshold, fixed volume subthreshold distension (122 (16) ml) was maintained for a 30 minute period before and after administration of neostigmine 0.5 mg intravenously. Mean intraballoon pressure, number, amplitude, and duration of contractions, and frequency of sensations were analysed. The period after neostigmine was divided into 10 second intervals and evaluated for the occurrence of contractions and onset of sensations. Fisher's exact test was applied to calculate the sensation-contraction association probability (SAP) as (1.0-p)x100%. RESULTS: Neostigmine increased intraballoon pressure (p<0.01), number of contractions (p<0.01), and number of sensations (p<0.01) per minute in all subjects. In seven of 10 subjects a significant association (SAP >95%) was found between sensations and contractions. In the remaining subjects, contractions were not associated with sensations and had lower amplitude (p<0.05) and duration (p<0.01) compared with contractions in the other seven subjects. CONCLUSION: In humans, tension receptors are involved in mediating colonic mechanosensitivity.

Raltitrexed plus gemcitabine (TOMGEM) in advanced pancreatic cancer. Results of a Belgian multicentre phase II study.

OBJECTIVES: This multicenter phase II study was designed to determine the activity and tolerance of gemcitabine and raltitrexed in advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Thirty-three chemonaive patients with measurable disease received the TOMGEM regimen consisting of Raltitrexed 3 mg/m(2) in 15 min followed by Gemcitabine 1,000 mg/m(2) in 30 min on day 1, Gemcitabine alone 1,000 mg/m(2) on day 8 and repeated on day 21. RESULTS: Thirty-three patients (median age: 62; locally advanced/metastatic disease: 5/28) were enrolled; the total number of cycles administered was 173 (median: 4). There were 10 partial response (confirmed), 2 stable disease (SD) >/=24 weeks, 7 SD <24 weeks, and 14 progressive disease for a response rate of 30.3% (95% CI: 14-46%); a clinical benefit was observed in 8/30 patients assessed (30%); median duration of response was 9.1 months. National Cancer Institute Common Toxicity Criteria grade III or IV neutropenia/thrombocytopenia were observed in 42 and 12% of the patients, respectively. Relevant nonhematological toxicities (grade III-IV) were rare although one toxic death was observed. Median time to progression was 2.8 months; one-year survival was 21%; median survival was 4.7 months. CONCLUSION: Our data suggest that the combination of raltitrexed/gemcitabine is a very convenient regimen with an acceptable toxicity, and is active in advanced pancreatic cancer.