Neil I. McDougall

Natural history of reflux oesophagitis: a 10 year follow up of its effect on patient symptomatology and quality of life.

BACKGROUND--Although oesophagitis is the most common diagnosis made at upper gastrointestinal endoscopy, data on the longterm outcome of affected patients are sparse. AIMS--This study assessed the level of reflux symptoms, quality of life, drug consumption, and complications in patients at least 10 years after diagnosis of oesophagitis at one centre. PATIENTS--One hundred and fifty two patients with typical reflux symptoms and a first time diagnosis by endoscopy of grade I-III oesophagitis between 1981 and 1984, were followed up using a postal questionnaire and telephone interview. RESULTS--Eighteen of 152 patients had died, 33 failed to respond, and 101 replied (mean follow up 11 years, range 121-160 months). Over 70% of patients still had heartburn at least daily (32%) or weekly (19%) or required daily acid suppression treatment (20%). Two patients (2%) had developed oesophageal strictures and one had Barretts oesophagus. Two of eight quality of life scores (physical function and social function) measured by the Short Form-36 were significantly lower than Northern Ireland population scores. CONCLUSION--Nearly three quarters of patients previously diagnosed as having oesophagitis still had significant morbidity related to gastro-oesophageal reflux disease more than 10 years after diagnosis. Some quality of life scores were significantly lower than those of the general population.

Safety and efficacy of combined use of sildenafil, bosentan, and iloprost before and after liver transplantation in severe portopulmonary hypertension†

Portopulmonary hypertension (PPHTN) represents a constrictive pulmonary vasculopathy in patients with portal hypertension. Liver transplantation (LT) may be curative and is usually restricted to patients with mild‐to‐moderate disease severity characterized by a mean pulmonary artery pressure (mPAP < 35 mm Hg). Patients with severe disease (mPAP > 50 mm Hg) are usually excluded from transplantation. We describe a patient with severe PPHTN, initiated on sequential and ultimately combination therapy of prostacyclin, sildenafil, and bosentan (PSB) pretransplantation and continued for 2 years posttransplantation. Peak mPAP on PSB therapy was dramatically reduced from 70 mm Hg to 32 mm Hg pretransplantation, and continued therapy facilitated a further fall in mPAP to 28 mm Hg posttransplantation. The pulmonary vascular resistance index fell from 604 to 291 dyne second−1 cm−5. The perioperative mPAP rose to 100 mm Hg following an episode of sepsis and fell with optimization of PSB therapy. In conclusion, this is the first reported patient with severe PPHTN using this combination of vasodilator therapy as a bridge to LT and then as maintenance in the posttransplantation phase. This regimen may enable LT in similar patients in the future, without long‐term consequences. Liver Transpl 14:287–291, 2008.

Randomized controlled trial assessing the effect of simvastatin in primary biliary cirrhosis.

This study evaluated the effect of statins in Primary biliary cirrhosis (PBC) on endothelial function, anti‐oxidant status and vascular compliance.

Primary biliary cirrhosis is associated with oxidative stress and endothelial dysfunction but not increased cardiovascular risk

Aim:  Primary biliary cirrhosis (PBC) is a chronic cholestatic disease which is associated with hypercholesterolaemia. Further, cholestatic diseases are associated with deficiencies of anti‐oxidant vitamins. Despite these associations PBC is not associated with an increase in cardiovascular mortality. The aim of this study is to assess if primary biliary cirrhosis is associated with oxidative stress, endothelial dysfunction and alteration of vascular compliance which is a surrogate marker for cardiovascular risk.

Maintenance therapy with cisapride after healing of erosive oesophagitis: a double‐blind placebo‐controlled trial

There are few data on the role of prokinetic agents as maintenance therapy in moderately severe reflux oesophagitis despite the high relapse rate of this condition after healing.

Microsatellite analysis provides evidence of neoplastic transformation in long‐segment, but not in short‐segment, Barrett's oesophagus

It has been suggested that the high prevalence of short segments of specialised intestinal metaplasia (SIM) at the gastro‐oesophageal junction is associated with the rising incidence of oesophageal adenocarcinoma. Our aims were to document the prevalence of short segments of SIM at the gastro‐oesophageal junction in patients attending for routine endoscopy and to determine if there was molecular evidence of neoplastic transformation in those with SIM. Patients (n = 101) were recruited from randomly selected upper gastro‐intestinal endoscopy lists. Biopsy specimens were taken at the squamo‐columnar junction to assess the prevalence of SIM. Frozen sections were assessed for molecular evidence of neoplastic transformation using microsatellite analysis. Squamo‐columnar biopsies were suitable for analysis in 95 patients, of whom 20 (21%) had oesophagitis and 2 (2%) had Barretts oesophagus (>3 cm of endoscopically apparent columnar‐lined oesophagus). Twenty patients had SIM at the gastro‐oesophageal junction, including 2 with Barretts oesophagus and 18 with short segments of SIM, one of whom had an associated intramucosal adenocarcinoma detected incidentally by histology. Three of the 20 cases with SIM exhibited novel microsatellite alleles, 2 with Barretts oesophagus and 1 with short segment SIM and an associated adenocarcinoma. The 18 patients with short segments of SIM at the gastro‐oesophageal junction were significantly older than those without SIM. Int. J. Cancer 85:482–485, 2000.

An audit of the role of ambulatory oesophageal pH monitoring in clinical practice

Objectives To audit the results and management outcomes resulting from 102 clinical referrals to a regional service for ambulatory oesophageal pH monitoring. In addition, the cost per case where management was influenced and cost of pH monitoring were assessed. Design and methods Retrospective review by two independent clinicians of the hospital charts of consecutive patients (n=102) who were referred for pH monitoring between November 1988 and November 1990. Results Oesophageal pH monitoring was normal in 46 (45%) patients, abnormal in 54 (53%) and two studies (2%) were unsuccessful. Eighty-six patients (84%) had undergone upper gastrointestinal endoscopy prior to monitoring, of which 44 were normal and 42 showed oesophagitis (11 grade I, 24 grades II-III and seven grade IV). Of the 44 patients with normal endoscopic findings, 18 (41%) had an abnormal monitoring result compared with 71% of those with endoscopic evidence of reflux disease (P= 0.0012). Management was influenced by monitoring in 68% of patients with normal endoscopy compared with 43% of those with oesophagitis (P= 0.032). Each pH monitoring study cost £24.96 and the overall cost per case where management was influenced by monitoring was £45.46. When divided into three groups according to prior endoscopy results, the cost per case where management was influenced was £36.61 in those with prior normal endoscopy, £49.92 in the group of 16 patients who did not have endoscopy, and £58.24 in those who had previously demonstrated oesophagitis. Conclusion Ambulatory oesophageal pH monitoring is a clinically useful and cost-effective test in patients with gastro-oesophageal reflux disease, particularly those with no endoscopic evidence of oesophagitis.

4640 A prospective randomised controlled trial of prophylactic versus symptomatic plastic stent exchange for palliation of malignant biliary obstruction.

Background: Endoscopic stent insertion is the optimum method of palliation for malignant biliary obstruction. Plastic stents are much cheaper than the metal alternatives which are only cost effective in longer surviving patients. However plastic stents are prone to occlusion and the optimal strategy for replacement of plastic stents prior to occlusion remains uncertain. Aim: To compare the outcome of patients with inoperable malignant biliary obstruction palliated by either elective plastic stent exchange or symptomatic exchange when the stent occludes. Methods: Patients with inoperable malignant biliary obstruction that had been successfully treated by ERCP and plastic stent insertion were recruited from 3 centres. They were randomised to either elective plastic stent exchange every 3 months or exchange when symptoms suggestive of stent obstruction developed. All patients were followed up for a minimum of 4 months or until death. Results: Forty patients (18 male, mean age 75 yrs (range 47-90 yrs) were randomised to one of two groups: symptomatic (n=18) or elective (n=22) stent replacement. The cause of biliary stricture was pancreatic cancer in 21 cases, cholangiocarcinoma in 16, ampullary tumor in 2 and metastases in 1. The median follow-up period was 117 days (range 2 435 days) and 34 patients died during follow-up. Overall survival rates were 88%, 63% and 30% at 30, 90 and 180 days. Only 8 (36%) of the elective group actually underwent elective replacement at 3 months, the remainder died before exchange (8), refused exchange (2), occluded before exchange (1) or were unfit for procedure (3). In total, 18 repeat ERCPs were performed in the elective group and 6 in the symptomatic group (p=0.26). Treatment group did not significantly effect survival rates or frequency of stent exchange. Kaplan-Meier analysis showed no significant difference in survival between the two treatment groups (p=0.87). Conclusions: A strategy to electively replace plastic stents in patients with inoperable malignant biliary obstruction does not significantly improve patient survival and is only likely to impact on a minority of patients due to the generally poor survival of such cohorts.

Association of symptoms with acid reflux during esophageal pH monitoring.

tryptase in H. pylor/-positive as compared to H. pylori-negative patients; a similar trend, although not statistically significant, was observed also for antral tryptase (Table 1). No significant differences were found for body and antral tryptase levels of patients with active as compared to patients with healed gastric or duodenal ulcer (gastric ulcer: t = 0.37, P = NS and t = 1.47, P = NS; duodenal ulcer: t = 0.40, P = ns and t = 0.41, P = ns for body and antral levels, respectively). Furthermore, a correlation was found between antral mucosal levels of tryptase and gastrin (r = 0.422, P < 0.001). Our findings suggest that H. pylori interacts with mucosHI-type mast cells in humans, especially in the oxyntic gastric area. The link found between tryptase and gastrin, which acts on histaminergic and cholinergic neurons (2), suggests that H. pylori may induce histamine and tryptase release from mucosal mast cells, which lie in close proximity to mucosal nerves, by an indirect gastrin stimulation, whereas in the paper of Bechi et al (1) a direct mechanism of potentiation of histamine release from serosal mast cells is advocated. MARIO PLEBANI, MD DANIELA BASSO, MD Institute of Laboratory Medicine University of Padova, Italy FABIO VIANELLO, MD FRANCESCO DI MARIO, MD Department of Gastroenterology University of Padova, Italy

Endothelial function, antioxidant status and vascular compliance in newly diagnosed HFE C282Y homozygotes.

PURPOSE This pilot study was aimed to establish techniques for assessing and observing trends in endothelial function, antioxidant status and vascular compliance in newly diagnosed HFE haemochromatosis during the first year of venesection. PATIENTS/METHODS Untreated newly diagnosed HFE haemochromatosis patients were tested for baseline liver function, iron indices, lipid profile, markers of endothelial function, anti-oxidant status and vascular compliance. Following baseline assessment, subjects attended at 6-weeks and at 3, 6, 9 and 12-months for follow-up studies. RESULTS Ten patients were recruited (M=8, F=2, mean age=51 years). Venesection significantly increased high density lipoproteins at 12-months (1.25 mmol/L vs. 1.37 mmol/L, p=0.01). However, venesection did not significantly affect lipid hydroperoxides, intracellular and vascular cell adhesion molecules or high sensitivity C-reactive protein (0.57 μmol/L vs. 0.51 μmol/L, p=0.45, 427.4 ng/ml vs. 307.22 ng/ml, p=0.54, 517.70 ng/ml vs. 377.50 ng/ml, p=0.51 and 290.75 μg/dL vs. 224.26 μg/dL, p=0.25). There was also no significant effect of venesection on anti-oxidant status or pulse wave velocity (9.65 m/s vs. 8.74 m/s, p=0.34). CONCLUSIONS Venesection significantly reduced high density lipoproteins but was not associated with significant changes in endothelial function, anti-oxidant status or vascular compliance. Larger studies using this established methodology are required to clarify this relationship further.