European Society of Coloproctology Colorectal Robotic Surgery Training for the Trainers Course - the first pilot experience.

AIM: Currently, there is no established colorectal specific robotic surgery Train the Trainer (TTT) course. The aim was to develop and evaluate such a course which can then be further developed to be incorporated within the planned European Society of Coloproctology (ESCP)/European School of Coloproctology (ESC) robotic colorectal surgery training curriculum. METHOD: After identifying the need for such a course within a training programme, the course was developed by a subgroup of the ESCP/ESC. A scoping literature review was performed and the content and materials for the course were developed by a team consisting of two gastroenterologists with a combined experience of 30 years of facilitating TTT courses, a robotic surgeon and proctor with laparoscopic TTT faculty experience and experienced robotic and laparoscopic colorectal trainers. The course was evaluated by asking delegates to complete pre- and post-course questionnaires. RESULTS: There were eight delegates on the course from across Europe. Delegates increased their knowledge of each of the course learning objectives and identified learning points in order to change practice. The feedback from the delegates of the course was positive across several areas and all felt that they had achieved their own personal objectives in attending the course. CONCLUSION: This pilot robotic colorectal TTT course has achieved its aim and demonstrated many positives. There is a need for such a course and the evaluation processes have provided opportunities for reflection, which will allow the development/tailoring of future robotic colorectal TTT courses to help develop robotic training further.

Risk factors for complication following ERCP; results of a large-scale, prospective multicenter study.

BACKGROUND AND STUDY AIMS: Analyses of endoscopic retrograde cholangiopancreatography (ERCP) complication are often constrained by the number of endpoints observed. This large-scale study aimed to identify the principal risk factors for ERCP complication. PATIENTS AND METHODS: This was a prospective multicenter study of ERCP complications, based in five English regions. An exploratory univariable analysis of patients' first recorded procedures identified potentially important patient- and procedure-related factors. For overall complications and pancreatitis, variables significant in univariable analysis were included in multiple regression. RESULTS: A total of 66 centers collected data on 5264 ERCPs, performed on 4561 patients. A therapeutic intervention was attempted in 3447/4561 (76%) of patients as part of their first recorded ERCP. Following first recorded ERCP, 230 patients (5.0%) suffered > or = 1 complication: pancreatitis in 74 (1.6%), cholangitis in 48 (1.0 %), hemorrhage in 40 (0.9%), perforation in 20 (0.4%), and miscellaneous in 54 (1.2%). Significant factors from multiple regression were included in a multi-level analysis, which incorporated variables measured at the level of the endoscopist and hospital. For overall complication, risk factors ( P value, odds ratio [OR], 95% confidence interval [CI]) were: cannulation attempts > 1 ( P = 0.094, OR 1.32, 95% CI 0.95-1.83), precut ( P = 0.033, OR 1.55, 95 % CI 1.04-2.32), and suspected sphincter of Oddi dysfunction ( P = 0.121, OR 1.97, 95 % CI 0.84-4.64). For pancreatitis, risk factors ( Pvalue, OR, and 95 % CI) were: cannulation attempts > 1 ( P = 0.0001, OR 3.14, 95% CI 1.74-5.67), female sex ( P < 0.001, OR 2.22, 95% CI 1.43-3.45), age ( P < 0.002, OR 1.09 per 5 year decrease, 95% CI 1.03-1.15), and performance in a district (as opposed to university) hospital ( P = 0.034, OR 2.41, 95% CI 1.08-5.41). CONCLUSION: Careful patient selection combined with skilled cannulation minimizes complications. Higher-risk procedures should be performed in specialist centers.

Variations in the reporting of endoscopies by different endoscopists.

All gastroscopies and colonoscopies performed in two U.K. teaching hospitals over a period of one year were audited to investigate whether endoscopic reporting of gastroscopies and colonoscopies by different endoscopists is consistent. Endoscopic diagnoses were retrieved from the hospitals' endoscopy databases. The results of 1814 colonoscopies and 2127 gastroscopies were analysed using chi2 (Chi squared). The frequency of reporting common diagnoses was variable and the differences between specialist endoscopists were highly significant, including for important conditions such as peptic ulceration (range 2-10%, p = 0.001) and colonic polyps (16-45%, p < 0.001). There is a large variation in the frequency of the diagnoses reported by different endoscopists. This is unlikely to be explained by casemix or chance. This may have major implications for the health of patients. More emphasis must be placed during training on the correct interpretation of endoscopies.

A questionnaire study to assess long-term outcome in patients with abnormal esophageal manometry.

Patients with unexplained chest pain or dysphagia are often referred for esophageal manometric studies to further investigate their symptoms. Four main manometric abnormalities have been described: achalasia, diffuse esophageal spasm, "nutcracker" (hypercontracting) esophagus, and hypocontracting esophagus. With the exception of achalasia, treatments are of limited benefit and the natural history of these conditions is largely unknown. We sent questionnaires to patients who were investigated at least three years before our study began. They repeated a DeMeester symptom questionnaire that they had completed at the time of their initial study. Questionnaires were sent to 137 patients with diffuse esophageal spasm, "nutcracker" (hypercontracting) esophagus, or hypocontracting esophagus. We also sent questionnaires to 57 patients with dysphagia or chest pain who had had normal esophageal manometry and pH studies. These patients acted as symptomatic controls. Responses were compared using the Wilcoxon signed ranks test. Seventy-two (53%) patients with diffuse esophageal spasm, "nutcracker" esophagus, or hypocontracting esophagus replied. An additional 8 (6%) patients died. Symptom scores in all three conditions had improved significantly over time (p < or = 0.01 for each condition, Wilcoxon signed ranks test). Patients with dysphagia or chest pain but normal esophageal studies had not improved. The significance of diffuse esophageal spasm, "nutcracker" esophagus, and hypocontracting esophagus found at esophageal manometry remains uncertain. Although treatment is often ineffective, these conditions typically run a benign course. Patients can be reassured that their symptoms are likely to improve with time.

Self-expanding metal stents in the palliation of malignant dysphagia: outcome analysis in 100 consecutive patients.

SUMMARY. Patients with inoperable esophageal malignancy often undergo palliative self-expanding metal stent insertion. This analysis of cases shows that although such stents provide good palliation of dysphagia, complications frequently occur. Complications reported were pain after insertion, bleeding, food bolus impaction, stent migration and increased gastroesophageal reflux. Furthermore, in patients with esophageal adenocarcinoma, survival was less if the distal end of the stent entered the stomach, rather than lying entirely within the esophagus. Reduced survival, in this group with gastroesophageal junction tumors, may be a result of increased gastroesophageal reflux leading to pulmonary aspiration. Stents incorporating an antireflux valve have been shown to reduce symptomatic gastroesophageal reflux. It may be that such valves offer a survival advantage where stent insertion ablates the function of the lower esophageal sphincter. Further studies are needed to assess the role of antireflux stents on survival in patients with gastroesophageal junction tumors.

Cell cycle regulation in patients with intestinal metaplasia at the gastro-oesophageal junction.

BACKGROUND/AIMS: The incidence of oesophageal adenocarcinoma is increasing rapidly and this may be related to the presence of intestinal metaplasia (IM) at the gastro-oesophageal junction (GOJ). Recent studies have distinguished two subtypes of IM at the GOJ: short segment Barrett's oesophagus (SSBO) and IM at a normal squamo-columnar junction (IMNSCJ). Because abnormal expression of cell cycle regulators is common in cancer and precancerous states, cell cycle regulation was studied in patients with IM at the GOJ. METHODS: Biopsy samples and resected materials were identified from patients with SSBO (10), IMNSCJ (14), a normal SCJ with (14) and without (12) inflammation, conventional Barrett's oesophagus (BO) (12), and oesophageal adenocarcinoma (12). Sections were stained with antibodies to p21, p27, p53, Ki67, cyclin D1, and c-erbB2 and were assessed independently by two observers, using predetermined criteria. RESULTS: Patients with oesophageal adenocarcinoma showed high expression of c-erbB2, p53, p27, and Ki67. Patients with BO showed expression of c-erbB2 but little expression of other markers. Greatly increased expression of cyclin D1 was seen in patients with IMNSCJ. The expression of all other markers was similar in patients with IMNSCJ and those with SSBO. Cyclin D1 and c-erbB-2 were coexpressed in patients with SSBO and IMNSCJ, and their expression was associated with the presence of p53 and p21. CONCLUSIONS: Although the proposed aetiologies of SSBO (gastro-oesophageal reflux) and IMNSCJ (Helicobacter pylori infection) differ, the cell cycle response is similar and both may have malignant potential.

Studies of compliance with delayed-release mesalazine therapy in patients with inflammatory bowel disease.

BACKGROUND: Non-compliance with maintenance mesalazine therapy may be a risk factor for relapse in inflammatory bowel disease, but the prevalence and determinants of non-compliance are unknown. AIM: To study the prevalence and determinants of non-compliance in patients with inflammatory bowel disease. METHODS: Out-patients receiving delayed-release mesalazine were studied. Compliance was determined by direct enquiry and by analysis of urine samples for 5-aminosalicylic acid/N-acetyl-5-aminosalicylic acid. Potential determinants of compliance were assessed. RESULTS: Ninety-eight patients were studied. Forty-two patients (43%) reported taking <80% of their prescribed dose. Logistic regression revealed the independent predictors of non-compliance to be three-times daily dosing [odds ratio (OR), 3.1; 95% confidence interval (CI), 1.8-8.4] and full-time employment (OR, 2.7; 95% CI, 1.1-6.9). Urine from 12 patients (12%) contained no detectable 5-aminosalicylic acid/N-acetyl-5-aminosalicylic acid, and 18 patients (18%) had levels below those expected. Depression was the only independent predictor of complete non-compliance (OR, 10.5; 95% CI, 1.8-79.0), and three-times daily dosing was the only independent predictor of partial non-compliance (OR, 3.7; 95% CI, 1.8-8.9). Self-reporting correctly identified 66% of patients judged to be non-compliant on urinary drug measurement. CONCLUSIONS: Non-compliance with maintenance mesalazine therapy is common in patients with inflammatory bowel disease. Three-times daily dosing and full-time employment are predictors of partial non-compliance, whilst depression is associated with complete non-compliance. Self-reporting detects most non-compliant patients.

Genetic influences in gastro-oesophageal reflux disease: a twin study.

BACKGROUND: A number of families have been described which include multiple members with symptomatic, endoscopic, or complicated gastro-oesophageal reflux disease (GORD). First degree relatives of patients with GORD are more likely to suffer with GORD symptoms. These observations raise the possibility of a genetic contribution to the aetiology of GORD. AIMS: To determine the relative contribution of genetic factors to GORD by evaluating GORD symptoms in monozygotic (MZ) and dizygotic (DZ) twins. METHODS: A total of 4480 unselected twin pairs, identified from a national volunteer twin register, were asked to complete a validated symptom questionnaire. GORD was defined as symptoms of heartburn or acid regurgitation at least weekly during the past year. RESULTS: Replies were obtained from 5032 subjects (56% response rate). A total of 1960 twin pairs were evaluable: 928 MZ pairs (86 male pairs, mean (SD) age 52 (13) (range 19-81) years) and 1032 DZ pairs (71 male pairs, mean age 52 (13) (20-82) years). The prevalence of GORD among both groups of twins was 18%. Casewise concordance rates were significantly higher for MZ than DZ twins (42% v 26%; p<0.001). Multifactorial liability threshold modelling suggests that additive genetic effects combined with unique environmental factors provide the best model for GORD. Heritability estimates suggest that 43% (95% confidence interval 32-55%) of the variance in liability to GORD is due to additive genetic factors. CONCLUSIONS: There is a substantial genetic contribution to the aetiology of GORD.

Axillary vein thrombosis in a healthy donor following platelet apheresis.

Platelet donation is a common and usually safe procedure accounting for almost half of the platelets donated in the UK. We describe a previously healthy female donor who developed an axillary vein thrombosis following an apheresis platelet donation.

The effect of cholecystokinin antagonism on postprandial lower oesophageal sphincter function in asymptomatic volunteers and patients with reflux disease.

BACKGROUND: Postprandial acid reflux is thought to be mediated by the increase in transient lower oesophageal sphincter relaxations (TLOSR) frequency and fall in lower oesophageal sphincter (LOS) pressure seen after ingestion of a meal. Studies in animals and healthy volunteers suggest that cholecystokinin (CCK) may play a role. AIM: To study the role of CCK in postprandial LOS function using the CCK antagonist loxiglumide. SUBJECTS: 10 asymptomatic volunteers (7 male, 20-29 years) and 9 patients with symptomatic gastro-oesophageal reflux (4 male, 33-66 years). METHODS: Oesophageal, LOS and gastric pressure and oesophageal pH readings were recorded for 1 h before and 2 h after intragastric infusion of a 200 kCal, 300 mL long chain triglyceride meal. Each subject underwent two studies and received intravenous loxiglumide or placebo infusion in randomized order. RESULTS: During placebo infusion, postprandial LOS pressure fell [volunteers: 17 (9-31) to 7 (1-19) mmHg (P < 0.01), patients: 15 (6-26) to 9 (2-21) mmHg (P=0.02)] and TLOSR frequency increased [volunteers: 0 (0-1) to 2 (0-7) per hour (P=0.01), patients: 0 (0-3) to 2 (0-10) per hour (P=0.03)]. Loxiglumide infusion attenuated the postprandial fall in LOS pressure and the postprandial increase in TLOSR frequency [volunteers: 0 (0-3) per hour (P=0.04 vs. placebo), patients: 0 (0-2) per hour (P=0.03 vs. placebo)], but it had only modest effects on postprandial acid exposure [volunteers: placebo 45 (0-1725) vs. loxiglumide 0 (0-443) seconds (N.S.), patients: placebo 60 (0-3442) seconds vs. loxiglumide 31 (0-1472) seconds (N.S.)]. CONCLUSIONS: Loxiglumide inhibits TLOSR and attenuates the fall in LOS pressure following a meal, but has only modest effects on postprandial gastro-oesophageal acid reflux.

Transient lower esophageal sphincter relaxations are no more frequent in patients with gastroesophageal reflux disease than in asymptomatic volunteers.

OBJECTIVES: Studies of the relative frequency of transient lower esophageal sphincter relaxations (TLESRs) in patients with gastroesophageal reflux disease and asymptomatic controls have revealed conflicting data. We have therefore studied the frequency of TLESRs and the frequency and mechanisms of acid reflux episodes in patients with gastroesophageal reflux disease and age- and sex-matched asymptomatic controls using standardized criteria. METHODS: Ten patients with symptomatic gastroesophageal reflux disease (four male, aged 50 [30-59] yr) and 10 asymptomatic matched volunteers (four male, aged 50 [32-59] yr) were studied. Esophageal, lower esophageal sphincter, and gastric manometric and esophageal pH readings were recorded for 1 h before and 1 h after a 200-kcal, 150 ml long-chain triglyceride meal. RESULTS: TLESR frequency increased after the meal in both volunteers (median 0 [range = 0-3] to 3 [0-8] per hour,p < 0.01) and patients (1 [0-6] to 2.5 [0-9] per hour, p = 0.08). There was no significant difference in the frequency of TLESRs between volunteers and patients. TLESRs were more likely to be associated with acid reflux in patients (65% vs 37%, p = 0.03), whereas volunteers were more likely to reflux gas or liquid without acid (30% vs 3.0%, p = 0.01). CONCLUSIONS: TLESRs are no more frequent in patients with gastroesophageal reflux disease than age- and sex-matched asymptomatic volunteers. However, when TLESRs occur in patients, they are twice as likely to be associated with acid reflux.

Once versus divided daily dosing with delayed-release mesalazine: a study of tissue drug concentrations and standard pharmacokinetic parameters.

BACKGROUND: Delayed-release mesalazine is traditionally taken as three divided doses. However, it is well-recognized that dosing frequency has a significant impact on compliance and that once daily dosing is preferable. METHODS: We measured serum, urinary, faecal and rectal tissue concentrations of 5-aminosalicylic acid and N-acetyl 5-aminosalicylic acid in 24 healthy volunteers following dosing with delayed-release mesalazine, 1.2 g or 2.4 g daily, given as either a single daily dose at 08:00 hours or in three divided doses at 08:00, 13:00 and 18:00 hours. RESULTS: Urinary and faecal excretion and rectal tissue concentrations of 5-aminosalicylic acid and N-acetyl 5-aminosalicylic acid were similar following single or divided daily dosing, at both doses studied. Peak serum concentrations were found at 06:00-09:00 following divided dosing and at 17:00-20:00 following once daily dosing. However, peak and trough serum levels and serum area under curve values (AUC) were similar with both regimens and at both doses. CONCLUSIONS: Urinary, faecal and rectal tissue concentrations are similar following single or divided daily dosing. Minor differences in serum levels were apparent but maximum, minimum and AUC values were similar. Clinical trials should examine the efficacy and toxicity of once daily dosing in patients with ulcerative colitis.

Magnetic resonance imaging of electroconvection in a polar organic solvent.

Molecular motion in the polar organic solvent nitrobenzene induced by an electric field is studied by magnetic resonance imaging. Rf pulse sequences that correlate images obtained at two different times under conditions of both continuous and pulsed electric fields are introduced. The resultant image correlation spectra indicate that the time scale of motion in a 9.6 kV/cm electric field is tens of milliseconds. Comparison of the results to an analytic solution for the Fokker-Planck probability function for one-dimensional bounded diffusion yields an electric field dependent effective diffusion coefficient for perdeuterated nitrobenzene of D = 1.08 x 10(-5) cm(2)/s + (3.33 x 10(-3) cm(4)/kV(2)s) E(2) at room temperature. Characteristics of this electroconvection and its consequences for combining multidimensional nuclear magnetic resonance with electrical orientation are also discussed.

Dose loading with delayed-release mesalazine: a study of tissue drug concentrations and standard pharmacokinetic parameters.

AIMS: Tissue concentrations of 5-aminosalicylic acid (5ASA) and its metabolites may influence the clinical course of inflammatory bowel disease. Since the factors that determine tissue drug concentrations are unknown we have studied the relationships between the oral dose of delayed-release mesalazine, rectal tissue drug concentrations and standard pharmacokinetic parameters. METHODS: Twelve healthy volunteers were studied following 7 days treatment with 1.2, 2.4 and 4.8 g of delayed-release mesalazine daily. 5-aminosalicylic acid and N-acetyl 5-aminosalicylic acid concentrations were measured in serum, urine, stool and rectal tissue biopsies. RESULTS: Serum concentrations and 24 h urinary excretion of 5ASA and N-acetyl 5ASA increased as the oral dose of mesalazine was increased from 1.2 g through 2.4 g to 4.8 g daily (serum area under curve (AUC):5ASA = 3. 9, 15.4 and 46.8 microg ml-1 h, P < 0.0001; N-acetyl 5ASA = 17.2, 30. 9 and 57.8 microg ml-1 h, P < 0.0001: urinary excretion: 5ASA = 1.8, 85.5 and 445 mg, P < 0.0001; N-acetyl 5ASA = 250, 524 and 1468 mg, P < 0.0001, respectively). Faecal 5ASA excretion increased as the oral dose increased from 1.2 g to 2.4 g but did not increase further with 4.8 g daily dosing whereas faecal N-acetyl 5ASA excretion was similar at all three doses. Rectal tissue concentrations of 5ASA increased markedly, and N-acetyl 5ASA increased modestly, as the dose of oral mesalazine increased from 1.2 g to 2.4 g daily but neither increased further with 4.8 g daily dosing. CONCLUSIONS: The relationship between the ingested dose of delayed-release mesalazine and rectal tissue drug concentrations is complex. Factors other than dose are likely to be important determinants of rectal tissue drug concentrations.

Monitoring the lower oesophageal sphincter: sphinctometer or sleeve?

Two methods have been used to study lower oesophageal sphincter (LOS) function in gastro-oesophageal reflux disease: the sleeve sensor and the sphinctometer. Our aim was to directly compare the sleeve and sphinctometer in vivo. Ten asymptomatic volunteers were intubated with a perfused assembly incorporating a sleeve sensor, a solid-state assembly incorporating a sphinctometer and a pH probe. LOS function was recorded pre- and post-prandially. During basal periods sleeve and sphinctometer readings correlated well both within and between subjects (r2 = 0.89 (P < 0.0001)). However, the sphinctometer relaxed less during swallows (median 42 (interquartile range 27-55)% vs 73 (62-81)% (P < 0.001)), transient LOS relaxations (TLOSR) (50 (40-70)% vs 94 (88-100)% (P < 0.001)) and reflux episodes (67 (59-75)% vs 97 (91-100)% (P = 0.02)). Using criteria derived from 10 dry swallows, the expected relaxation of the sphinctometer during TLOSR was defined. The sphinctometer had an overall sensitivity ranging from 43 to 71% for the detection of TLOSR with 11-22 false positive relaxations, depending on the criteria employed. Sensitivity was particularly poor in those with low basal LOS pressure. The sphinctometer has a lower capacity to register LOS relaxations than the sleeve sensor, which limits its value in studying the pathophysiology of reflux disease.

Familial clustering of reflux symptoms.

OBJECTIVE: A number of case reports describe multiple family members with gastroesophageal reflux disease and Barrett' s esophagus. The wider importance of familial factors in gastroesophageal reflux disease has not been established. Therefore, we have studied the prevalence of reflux symptoms and medication use among relatives of patients with documented gastroesophageal reflux disease. METHODS: A postal questionnaire study of the first degree relatives of six groups of matched patients. The groups comprised patients with 1) no dyspeptic symptoms; 2) reflux symptoms and a normal pH study; 3) reflux symptoms, an abnormal pH study, and a lower esophageal sphincter (LOS) pressure more than 10 mm Hg; 4) reflux symptoms, an abnormal pH study, and a LOS pressure less than 10 mm Hg; 5) Barrett's esophagus; and 6) peptic stricture. RESULTS: Four hundred eighteen subjects replied (78% response). Infrequent reflux symptoms were equally common in all groups of relatives. Frequent reflux symptoms, however, were more common among relatives of patients with an abnormal pH study and normal (26%, p = 0.007) or low LOS pressure (27%, p = 0.01) or Barrett's esophagus (30%, p = 0.003), compared with relatives of nondyspeptic patients (9%). Frequent reflux symptoms were no more common among relatives of patients with a normal pH study (16%) or peptic stricture (18%). Reflux medication use showed a similar pattern. CONCLUSIONS: Familial clustering of reflux symptoms is seen in relatives of patients with reflux symptoms and increased esophageal acid exposure and in relatives of patients with Barrett's esophagus.